Acute Post-Surgical Pain

Iatrogenic Pathograph 14 Show in embeddings browser Pain Surgical Complication

Ask OpenScientist

Ask a research question about Acute Post-Surgical Pain. OpenScientist will conduct autonomous deep research using the Disorder Mechanisms Knowledge Base and PubMed literature (typically 10-30 minutes).

Submitting...

Do not include personal health information in your question. Questions and results are cached in your browser's local storage.

8
Pathophys.
3
Phenotypes
1
Gaps
14
Pathograph
6
Medical Actions
2
Datasets
2
Trials
13
References
?

Discussions and Knowledge Gaps

1
Can spinal-selective Hsp90 inhibition translate into a human opioid-sparing adjuvant for acute post-surgical pain, and does reducing acute pain intensity by this route lower the incidence of chronic post-surgical pain?
KNOWLEDGE GAP OPEN gap_apsp_hsp90_adjuvant_translation
Attached to
pathophysiology#Spinal Microglial Gating of Opioid Antinociception pathophysiology#Transition to Chronic Post-Surgical Pain
The Hsp90-adjuvant mechanism is established only in rodent incision models and is spinal-compartment-specific. Whether it is achievable and beneficial in humans - and whether better acute analgesia via this route reduces CPSP - is unknown.
⚙

Pathophysiology

8
Surgical Incision and Nociceptor Activation
The trigger. A surgical incision through skin, fascia, and muscle directly activates high-threshold A-delta and C-fiber nociceptors at the wound. In the Brennan rat plantar-incision model - the standard preclinical analogue of human post-surgical pain - a hindpaw incision produces reliable, quantifiable mechanical hyperalgesia lasting several days, with input carried by the sural and tibial nerves.
Nociceptor (A-delta / C-fiber primary afferent) CL:0000198 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Nociceptor (A-delta / C-fiber primary afferent), annotated with pain receptor cell (CL:0000198). CL:0000198 is a cell type from the Cell Ontology.
Skin and soft tissue at the surgical wound UBERON:0002097 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in Skin and soft tissue at the surgical wound, annotated with skin of body (UBERON:0002097). UBERON:0002097 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Inflammatory Mediator Release at the Wound
Acute post-surgical pain
Show evidence (2 references)
PMID:8783314 SUPPORT Model Organism
"a surgical incision of the rat foot causes a reliable and quantifiable mechanical hyperalgesia lasting for several days after surgery"
Establishes the trigger: surgical incision produces quantifiable mechanical hyperalgesia. Evidence source is MODEL_ORGANISM because this is the Brennan rat plantar-incision model, the standard preclinical analogue of acute post-surgical pain.
PMID:8783314 SUPPORT Model Organism
"This model should allow us to understand mechanisms of sensitization caused by surgery and investigate new therapies for postoperative pain in humans."
The authors frame the incision model as the tool for studying surgery-caused sensitization and testing postoperative-pain therapies, motivating its use throughout this entry.
Inflammatory Mediator Release at the Wound
The molecular amplifier. Incised and injured tissue and infiltrating immune cells release an inflammatory milieu (prostaglandins, bradykinin, protons, ATP, cytokines, and nerve growth factor). Receptors, mediators, and neurotransmitters driving sensitization after incision have been specifically characterized and are in part unique to incisional pain.
Skin and soft tissue at the surgical wound UBERON:0002097 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in Skin and soft tissue at the surgical wound, annotated with skin of body (UBERON:0002097). UBERON:0002097 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Peripheral Nociceptor Sensitization
Show evidence (1 reference)
PMID:29392204 SUPPORT Model Organism
"the role of certain receptors, mediators, and neurotransmitters involved in peripheral and central sensitization after incision were identified"
Supports characterized inflammatory mediators/receptors driving sensitization after incision. Evidence source is MODEL_ORGANISM because the snippet reports findings from rodent incision-model studies.
Peripheral Nociceptor Sensitization
The cellular amplifier. The inflammatory milieu lowers nociceptor activation threshold and raises excitability, producing primary hyperalgesia at and immediately around the wound. In the incision model, distinct areas around the wound show altered withdrawal thresholds reflecting this peripheral sensitization.
Sensitized nociceptor (A-delta / C-fiber primary afferent) CL:0000198 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Sensitized nociceptor (A-delta / C-fiber primary afferent), annotated with pain receptor cell (CL:0000198). CL:0000198 is a cell type from the Cell Ontology.
Skin and soft tissue at the surgical wound UBERON:0002097 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in Skin and soft tissue at the surgical wound, annotated with skin of body (UBERON:0002097). UBERON:0002097 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
NaV1.8-Mediated Peripheral Nociceptive Signal Propagation
Show evidence (1 reference)
PMID:8783314 SUPPORT Model Organism
"Distinct areas around the wound had different withdrawal thresholds during the study period."
Documents spatially graded threshold changes around the incision consistent with peripheral nociceptor sensitization. Evidence source MODEL_ORGANISM (Brennan rat incision model).
NaV1.8-Mediated Peripheral Nociceptive Signal Propagation
NaV1.8 voltage-gated sodium channels on peripheral pain-sensing neurons and dorsal-root-ganglion nociceptors sustain action-potential firing and transmit incisional pain signals toward the spinal cord. Human-neuron pharmacology identifies this peripheral signaling step as a tractable, non-opioid therapeutic target.
Peripheral nociceptor CL:0000198 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Peripheral nociceptor, annotated with pain receptor cell (CL:0000198). CL:0000198 is a cell type from the Cell Ontology.
NaV1.8 voltage-gated sodium channel activity GO:0005248 Gene Ontology (GO) Relation: this pathophysiological event involves this molecular function This pathophysiological event involves NaV1.8 voltage-gated sodium channel activity, annotated with voltage-gated sodium channel activity (GO:0005248). GO:0005248 is a molecular function from the Gene Ontology.
Downstream
Spinal Central Sensitization
Show evidence (1 reference)
PMID:39775738 SUPPORT In Vitro
"This novel allosteric mechanism results in tonic inhibition of NaV1.8 and reduces pain signals in primary human DRG sensory neurons."
Human dorsal-root-ganglion neuron electrophysiology directly supports NaV1.8-dependent peripheral pain-signal propagation and its inhibition by suzetrigine. The evidence source is IN_VITRO because the quoted experiment used primary human sensory neurons outside an intact organism.
Spinal Central Sensitization
The central effector. Sustained nociceptor barrage into the spinal dorsal horn triggers activity-dependent synaptic plasticity - a prolonged, reversible increase in the excitability and synaptic efficacy of central nociceptive neurons (central sensitization), with a major NMDA-receptor/glutamatergic component ("wind-up") and a contribution from activated dorsal-horn microglia. Clinically it manifests as pain hypersensitivity beyond the wound: dynamic tactile allodynia and secondary hyperalgesia. Post-surgical pain is one of the conditions in which central sensitization is an established contributor.
Spinal dorsal horn microglia CL:0000129 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Spinal dorsal horn microglia, annotated with microglial cell (CL:0000129). CL:0000129 is a cell type from the Cell Ontology.
Activity-dependent synaptic potentiation (central sensitization) GO:0060291 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased Activity-dependent synaptic potentiation (central sensitization), annotated with long-term synaptic potentiation (GO:0060291). GO:0060291 is a biological process from the Gene Ontology. ↑ INCREASED NMDA/glutamatergic signaling in the dorsal horn GO:0007215 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased NMDA/glutamatergic signaling in the dorsal horn, annotated with glutamate receptor signaling pathway (GO:0007215). GO:0007215 is a biological process from the Gene Ontology. ↑ INCREASED Dorsal-horn microglial activation GO:0001774 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased Dorsal-horn microglial activation, annotated with microglial cell activation (GO:0001774). GO:0001774 is a biological process from the Gene Ontology. ↑ INCREASED
Spinal cord dorsal horn UBERON:0002256 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in Spinal cord dorsal horn, annotated with dorsal horn of spinal cord (UBERON:0002256). UBERON:0002256 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Spinal Microglial Gating of Opioid Antinociception
Resolution with Wound Healing
Transition to Chronic Post-Surgical Pain
Allodynia and secondary hyperalgesia
Show evidence (3 references)
PMID:20961685 SUPPORT Human Clinical
"Nociceptor inputs can trigger a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways, the phenomenon of central sensitization."
Defines central sensitization as nociceptor-input-driven amplification in central pathways. Evidence source HUMAN_CLINICAL because the review grounds central sensitization in human volunteer studies and clinical cohorts.
PMID:20961685 SUPPORT Human Clinical
"Central sensitization manifests as pain hypersensitivity, particularly dynamic tactile allodynia, secondary punctate or pressure hyperalgesia"
Links central sensitization to allodynia and secondary hyperalgesia, the spread of pain beyond the wound seen after surgery.
PMID:29392204 SUPPORT Model Organism
"Preclinical studies in rodent models characterized responses of primary afferent nociceptors and dorsal horn neurons as one neural basis for pain behavior"
Identifies dorsal-horn neuron responses as a neural basis of postoperative pain behavior. Evidence source MODEL_ORGANISM because the snippet reports rodent incision-model findings.
Spinal Microglial Gating of Opioid Antinociception
A preclinical therapeutic vulnerability at the same spinal dorsal-horn / microglial substrate as the central-sensitization node (its inbound edge). In the paw-incision (post-surgical) pain model, spinal Hsp90 inhibition activates microglial Src kinase signaling that enhances mu-opioid-receptor antinociception, enabling an opioid dose-reduction strategy; better acute analgesia via this route is hypothesized to blunt the acute-to-chronic transition (its downstream edge). This node conforms to the `spinal_hsp90_opioid_enhancement` module. IMPORTANT: the evidence is preclinical (mouse, intrathecal/isoform-selective dosing) and spinal-compartment-specific - brain/systemic non-selective Hsp90 inhibition blocks opioid antinociception - so this is a research target, not established human therapy.
Spinal dorsal horn microglia CL:0000129 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Spinal dorsal horn microglia, annotated with microglial cell (CL:0000129). CL:0000129 is a cell type from the Cell Ontology.
Microglial modulation of spinal opioid antinociceptive signaling GO:0038003 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased Microglial modulation of spinal opioid antinociceptive signaling, annotated with G protein-coupled opioid receptor signaling pathway (GO:0038003). GO:0038003 is a biological process from the Gene Ontology. ↑ INCREASED
Spinal cord dorsal horn UBERON:0002256 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in Spinal cord dorsal horn, annotated with dorsal horn of spinal cord (UBERON:0002256). UBERON:0002256 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Transition to Chronic Post-Surgical Pain
Show evidence (2 references)
PMID:41031962 SUPPORT Model Organism
"The enhanced antinociception seen with 17-AAG was completely abolished in the inhibitor groups in tail-flick and paw-incision pain models"
Ties the module's opioid-enhancement mechanism directly to the paw-incision (post-surgical) pain model. Evidence source is MODEL_ORGANISM (mouse).
PMID:41031962 SUPPORT Model Organism
"colocalization of activated Src with microglia"
Localizes the enhancing Src signaling to microglia, the cellular substrate of this therapeutic-vulnerability node and the module conformance target.
Resolution with Wound Healing
The expected consequence. In most patients the sensitized state resolves as the surgical wound heals over days to weeks; only a minority progress to persistent pain.
Show evidence (1 reference)
PMID:16698416 SUPPORT Human Clinical
"Acute postoperative pain is followed by persistent pain in 10-50% of individuals after common operations"
The reported minority progressing to persistent pain implies that most patients do not develop chronic pain, but the quoted text does not directly establish wound healing as the mechanism of resolution; polarity is therefore PARTIAL.
Transition to Chronic Post-Surgical Pain
The adverse consequence. In a substantial minority the sensitized state persists as chronic post-surgical pain (CPSP) - reported in 10-50% of individuals after common operations, severe in ~2-10% - often with a neuropathic component from intraoperative nerve injury. The intensity of the acute pain is a key predictor of this transition, the rationale for aggressive, opioid-sparing acute pain control.
Downstream
Chronic post-surgical pain
Show evidence (4 references)
PMID:16698416 SUPPORT Human Clinical
"Acute postoperative pain is followed by persistent pain in 10-50% of individuals after common operations, such as groin hernia repair, breast and thoracic surgery, leg amputation, and coronary artery bypass surgery."
Quantifies the acute-to-chronic transition across common operations. Evidence source HUMAN_CLINICAL (human epidemiology in a clinical review).
PMID:16698416 SUPPORT Human Clinical
"the intensity of acute postoperative pain correlates with the risk of developing a persistent pain state"
States the central clinical link modeled by this node: acute pain intensity predicts CPSP, motivating aggressive acute analgesia.
PMID:16698416 SUPPORT Human Clinical
"Iatrogenic neuropathic pain is probably the most important cause of long-term postsurgical pain."
Attributes much long-term CPSP to iatrogenic neuropathic injury, the neuropathic component noted in this node.
+ 1 more reference
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Acute Post-Surgical Pain Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

3
Constitutional 2
Acute post-surgical pain HP:0012531 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Pain (HP:0012531), qualified as temporality acute. HP:0012531 is a phenotype from the Human Phenotype Ontology.
Temporal: ACUTE
Show evidence (1 reference)
PMID:39319373 SUPPORT Human Clinical
"Nearly half of adult patients undergoing surgery experience moderate or severe postoperative pain."
Provides a contemporary consensus-review estimate for clinically important acute postoperative pain in adults.
Chronic post-surgical pain Chronic pain HP:0012532 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Chronic pain (HP:0012532), qualified as temporality chronic. HP:0012532 is a phenotype from the Human Phenotype Ontology.
Temporal: CHRONIC
Show evidence (2 references)
PMID:16698416 SUPPORT Human Clinical
"Acute postoperative pain is followed by persistent pain in 10-50% of individuals after common operations"
Supports chronic post-surgical pain as a sequela in a substantial subset (10-50% across common operations). Frequency band omitted because the source reports a wide range rather than a single enum-mappable band.
PMID:38809229 SUPPORT Human Clinical
"CPSP was defined as chronic pain that developed or increased in intensity after the surgical procedure and is localized to the surgical field or within the innervation territory of a nerve in the surgical field, and has persisted for 3 months post-surgery, with the exclusion of other causes of pain."
Supports the three-month duration, surgical-field localization, and exclusion-of-other-causes scope of the chronic sequela.
Other 1
Allodynia and secondary hyperalgesia HP:0012533 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Allodynia (HP:0012533). HP:0012533 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:20961685 SUPPORT Human Clinical
"Central sensitization manifests as pain hypersensitivity, particularly dynamic tactile allodynia, secondary punctate or pressure hyperalgesia"
Maps allodynia and secondary hyperalgesia to central sensitization. Evidence source HUMAN_CLINICAL (human volunteer/cohort grounding in the cited review).
💊

Medical Actions

6
Multimodal (Opioid-Sparing) Analgesia
Action: Multimodal analgesia (pain management)NCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Multimodal analgesia (pain management), annotated with Pain Therapy (NCIT:C15180). NCIT:C15180 is a clinical intervention from the NCI Thesaurus. Ontology label: Pain Therapy NCIT:C15180
Combining analgesics and techniques with different mechanisms - non-opioid systemics (acetaminophen, NSAIDs/COX-2 inhibitors), regional/neuraxial local anesthesia, and adjuncts such as ketamine (modeled separately below) - to control acute pain while reducing opioid consumption and side effects and enhancing recovery.
Show evidence (2 references)
PMID:29392204 SUPPORT Human Clinical
"Scientific evidence is able to point towards useful (and less useful) elements of multimodal analgesia able to reduce opioid consumption, improve pain management, and enhance recovery."
Supports multimodal, opioid-sparing analgesia as the evidence-based approach. Evidence source HUMAN_CLINICAL (guideline/clinical-evidence synthesis).
PMID:39319373 SUPPORT Other
"use of multimodal analgesia, including regional anaesthesia; non-pharmacological strategies; safe use of opioids"
A contemporary multidisciplinary consensus endorses multimodal analgesia, regional techniques, non-pharmacological strategies, and safe opioid use. Evidence source is OTHER because the quoted claim is a Delphi consensus.
Local and Regional Analgesia
Action: Regional anesthesia procedureNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Regional anesthesia procedure (NCIT:C64381). NCIT:C64381 is a clinical intervention from the NCI Thesaurus. Ontology label: Regional Anesthesia Procedure NCIT:C64381
Regional techniques such as fascial-plane blocks can reduce early postoperative pain and opioid requirements for selected procedures. Technique selection is procedure-specific and requires trained staff and safety protocols.
Show evidence (1 reference)
PMID:41363869 SUPPORT Other
"For adults, the American Society of Anesthesiologists (Schaumburg, Illinois) Task Force on Perioperative Pain Management strongly recommends fascial plane blocks to reduce pain and/or opioid requirements in the first 24 h postoperatively for open cardiothoracic, abdominal, retroperitoneal, and..."
The current ASA practice guideline directly supports regional fascial-plane blocks for early postoperative pain and opioid reduction. Evidence source is OTHER because the quoted statement is a guideline recommendation.
Opioid Analgesic Therapy
Action: opioid analgesic agent therapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is opioid analgesic agent therapy, annotated with Pain Therapy (NCIT:C15180). NCIT:C15180 is a clinical intervention from the NCI Thesaurus. Ontology label: Pain Therapy NCIT:C15180
Agent: morphine CHEBI:17303 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses morphine (CHEBI:17303). CHEBI:17303 is a therapeutic agent from Chemical Entities of Biological Interest.
Mu-opioid agonists (e.g., morphine) can be used within multimodal care for moderate-to-severe acute post-surgical pain, but their adverse effects and persistent-use risk motivate safe-use and opioid-sparing strategies and, in preclinical research, opioid adjuvants.
Show evidence (1 reference)
PMID:39319373 SUPPORT Other
"use of multimodal analgesia, including regional anaesthesia; non-pharmacological strategies; safe use of opioids"
The multidisciplinary consensus explicitly places safe opioid use within a multimodal peri-operative pain strategy. Evidence source is OTHER because the quoted claim is a Delphi consensus.
NMDA-Antagonist Adjuvant (Ketamine)
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: ketamine CHEBI:6121 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses ketamine (CHEBI:6121). CHEBI:6121 is a therapeutic agent from Chemical Entities of Biological Interest.
Perioperative low-dose ketamine, an NMDA-receptor antagonist, acts on the spinal central-sensitization node (the NMDA/glutamatergic "wind-up" component), reducing postoperative pain and opioid consumption and contributing preventive analgesia.
Mechanism Target:
INHIBITS Spinal Central Sensitization — NMDA-receptor antagonism dampens the glutamatergic wind-up that drives spinal central sensitization, reducing pain and opioid requirement.
Show evidence (1 reference)
PMID:15105220 SUPPORT Human Clinical
"Dextromethorphan and ketamine were found to have significant immediate and preventive analgesic benefit in 67% and 58% of studies, respectively."
Supports ketamine (NMDA antagonist) reducing postoperative pain/analgesic consumption. Evidence source HUMAN_CLINICAL (qualitative systematic review of perioperative randomized trials).
Suzetrigine (NaV1.8 Inhibitor)
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: suzetrigine NCIT:C199115 NCI Thesaurus (NCIT) Relation: this treatment uses this therapeutic agent This treatment uses suzetrigine (NCIT:C199115). NCIT:C199115 is a therapeutic agent from the NCI Thesaurus.
Suzetrigine is an oral, first-in-class non-opioid analgesic for moderate-to-severe acute pain. It selectively inhibits peripheral NaV1.8 channels; two large phase III postoperative trials after abdominoplasty and bunionectomy showed clinically meaningful pain reduction versus placebo and pain reduction similar to hydrocodone/acetaminophen over 48 hours.
Mechanism Target:
INHIBITS NaV1.8-Mediated Peripheral Nociceptive Signal Propagation — Selective NaV1.8 inhibition reduces action-potential firing and pain-signal transmission in peripheral human dorsal-root-ganglion sensory neurons.
Show evidence (1 reference)
PMID:39775738 SUPPORT In Vitro
"This novel allosteric mechanism results in tonic inhibition of NaV1.8 and reduces pain signals in primary human DRG sensory neurons."
Human sensory-neuron electrophysiology directly supports the modeled mechanism target and inhibitory treatment effect.
Show evidence (1 reference)
PMID:40117446 SUPPORT Human Clinical
"As compared with placebo, suzetrigine reduced moderate-to-severe acute pain over 48 h after abdominoplasty or bunionectomy. Pain reduction with suzetrigine was similar to that with hydrocodone bitartrate/acetaminophen."
Two randomized, placebo- and active-controlled phase III postoperative-pain trials directly support clinical efficacy and appropriately limit the claim to the studied procedures and 48-hour endpoint.
Spinal-Selective Hsp90 Inhibitor (Preclinical Opioid Adjuvant)
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: 17-AAG (tanespimycin) CHEBI:64153 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses 17-AAG (tanespimycin), annotated with tanespimycin (CHEBI:64153). CHEBI:64153 is a therapeutic agent from Chemical Entities of Biological Interest.
A preclinical opioid-adjuvant strategy: spinal-cord-directed Hsp90 inhibition (intrathecal 17-AAG/tanespimycin, or spinal-selective Hsp90-beta/Grp94 inhibitors) enhances mu-opioid antinociception in the paw-incision (post-surgical) pain model via microglial Src signaling, enabling opioid dose reduction and tolerance rescue. NOT an established human therapy - effect is spinal-compartment-specific and demonstrated only in rodents.
Mechanism Target:
ACTIVATES Spinal Microglial Gating of Opioid Antinociception — Spinal Hsp90 inhibition activates the microglial Src signaling that gates enhanced opioid antinociception, potentiating analgesia and rescuing tolerance in the paw-incision model (conforms to the spinal_hsp90_opioid_enhancement module).
Show evidence (1 reference)
PMID:41031962 SUPPORT Model Organism
"The enhanced antinociception seen with 17-AAG was completely abolished in the inhibitor groups in tail-flick and paw-incision pain models"
Supports the adjuvant mechanism specifically in the paw-incision (post-surgical) model. Evidence source MODEL_ORGANISM (mouse); this is a preclinical research target, not established therapy.
🌍

Environmental Factors

2
Pre-existing pain and heightened pain sensitivity
Preoperative pain history and greater pain sensitivity are candidate risk-stratification domains for moderate-to-severe acute postsurgical pain.
Show evidence (1 reference)
PMID:38799277 SUPPORT Human Clinical
"This review investigates the risk factors for APSP, including gender, age, obesity, smoking history, preoperative pain history, pain sensitivity, preoperative anxiety, depression, pain catastrophizing, expected postoperative pain, surgical fear, and genetic polymorphisms."
The narrative review enumerates preoperative pain and pain sensitivity in its APSP risk-factor scope, but this abstract sentence does not quantify or independently confirm either association; polarity is therefore PARTIAL.
Psychological vulnerability before surgery
Preoperative anxiety, depression, pain catastrophizing, fear of surgery, and high expected postoperative pain are candidate psychological risk-stratification domains for acute postsurgical pain.
Show evidence (1 reference)
PMID:38799277 SUPPORT Human Clinical
"This review investigates the risk factors for APSP, including gender, age, obesity, smoking history, preoperative pain history, pain sensitivity, preoperative anxiety, depression, pain catastrophizing, expected postoperative pain, surgical fear, and genetic polymorphisms."
The narrative review enumerates these psychological variables in its APSP risk-factor scope, but this abstract sentence does not quantify or independently confirm each association; polarity is therefore PARTIAL.
🔬

Diagnosis

1
Function-guided peri-operative pain assessment
Repeated pain assessment across the peri-operative pathway should evaluate functional interference as well as pain intensity, guiding reassessment of analgesia rather than treating a unidimensional score alone.
Pain assessment NCIT:C20992 NCI Thesaurus (NCIT)
Results: Moderate or severe pain and pain that impairs recovery functions indicate inadequately controlled postoperative pain and the need to reassess the analgesic plan.
Show evidence (1 reference)
PMID:39319373 SUPPORT Other
"assessing pain to facilitate function; use of multimodal analgesia, including regional anaesthesia; non-pharmacological strategies; safe use of opioids; and use of protocols and training for staff in caring for patients with postoperative pain."
The multidisciplinary consensus explicitly makes function-facilitating pain assessment a generic principle. Evidence source is OTHER because the claim is a Delphi consensus recommendation rather than a patient-level study.
📊

Prevalence

1
Post-discharge surgical cohorts
Period Prevalence 44500.0 per 100,000 (31000.0–58000.0) Common
Conditional prevalence among people who underwent surgery, measured during the first 1-14 days after hospital discharge; this is not general-population prevalence.
Show evidence (1 reference)
PMID:37181639 SUPPORT Human Clinical
"Meta-analyses of combinable studies provided estimates of pooled prevalence rates of moderate-to-severe postoperative pain ranging from 31% 1 day after discharge to 58% 1 to 2 weeks after discharge."
Quantifies the common conditional prevalence of moderate-to-severe pain after discharge across 27 studies and 22,108 surgical participants.
📊

Related Datasets

2
A mouse model of acute post-surgical pain geo:GSE125076
Pain is the leading cause of disability in the developed world but remains a poorly treated condition. Specifically, post-surgical pain continues to be a frequent and undermanaged condition. Here, we investigate the analgesic potential of pharmacological NaV1.7 inhibition in a mouse model of acute post-surgical pain, based on incision of the plantar skin and underlying muscle of the hind paw. We demonstrate that local and systemic treatment with the selective NaV1.7 inhibitor μ-theraphotoxin-Pn3a is effectively anti-allodynic in this model and completely reverses mechanical hypersensitivity in the absence of motor adverse effects.
mouse BULK RNA SEQ n=6
PMID:31335646
Identified by GEO DataSets index search for Acute Post-Surgical Pain (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
Human birth tissue products as a regenerative medicine for post-surgical pain through multi-modal action geo:GSE242389
Post-surgical pain causes significant suffering. Extracts of the human amniotic membrane (AM) may be novel regenerative matrices, but little is known about their use in pain treatment. Locally applying FLO (particulates of AM) in mice acutely attenuated post-surgical pain hypersensitivity and inhibited its transition to a prolonged state after plantar-incision. Mechanistically, this was achieved through direct nociceptive neuronal inhibition via CD44-dependent mechanisms and indirect anti-pain effect by attenuating immune cell recruitment and promoting wound healing.
mouse BULK RNA SEQ n=6
PMID:39594635
Identified by GEO DataSets index search for Acute Post-Surgical Pain (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
🔬

Clinical Trials

2
NCT05558410 PHASE_III COMPLETED
Randomized, double-blind, placebo-controlled pivotal trial of suzetrigine for moderate-to-severe acute pain after abdominoplasty.
Target Phenotypes: Acute pain HP:0012531 Human Phenotype Ontology (HP) Relation: this clinical trial targets this phenotype This clinical trial targets Acute pain, annotated with Pain (HP:0012531), qualified as temporality acute. HP:0012531 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
clinicaltrials:NCT05558410 SUPPORT Human Clinical
"The purpose of this study was to evaluate the efficacy and safety of Suzetrigine (SUZ) in treating acute pain after an abdominoplasty."
ClinicalTrials.gov identifies this pivotal phase III postoperative-pain trial and its disease-relevant intervention and surgical setting.
NCT05553366 PHASE_III COMPLETED
Randomized, double-blind, placebo-controlled pivotal trial of suzetrigine for moderate-to-severe acute pain after bunionectomy.
Target Phenotypes: Acute pain HP:0012531 Human Phenotype Ontology (HP) Relation: this clinical trial targets this phenotype This clinical trial targets Acute pain, annotated with Pain (HP:0012531), qualified as temporality acute. HP:0012531 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
clinicaltrials:NCT05553366 SUPPORT Human Clinical
"The purpose of this study is to evaluate the efficacy and safety of suzetrigine for acute pain after a bunionectomy."
ClinicalTrials.gov identifies this pivotal phase III postoperative-pain trial and its disease-relevant intervention and surgical setting.
{ }

Source YAML

click to show 
name: Acute Post-Surgical Pain
creation_date: "2026-07-25T00:00:00Z"
category: Iatrogenic
disease_term:
  preferred_term: Acute post-surgical pain
  # No MONDO term: MONDO has no human "acute post-surgical pain" disease entity
  # and obsolete or non-human postoperative-pain mappings are not appropriate.
  # Left intentionally unbound per curation decision; the closest human MONDO
  # relative is MONDO:0024317 (chronic pain syndrome) and the chronic sequela is
  # recognized in ICD-11 as MG30.21 chronic postsurgical pain. A disease-level
  # ICD-11 mapping is deliberately NOT added: MG30.21 codes the CHRONIC entity,
  # so mapping this ACUTE entry to it would be semantically incorrect.
parents:
- Pain
- Surgical Complication
notes: >-
  Acute post-surgical (post-operative) pain is the nociceptive/inflammatory pain
  arising directly from surgical tissue injury, normally resolving as the wound
  heals (days to weeks). It is common after surgery and clinically
  important out of proportion to its transience because its intensity is a
  leading predictor of the transition to chronic post-surgical pain (CPSP; ICD-11
  MG30.21). The pathophysiology chain here (incision -> inflammatory mediator
  release -> peripheral nociceptor sensitization -> spinal central sensitization
  -> resolution vs. transition to chronic post-surgical pain) is the substrate on
  which opioid-sparing multimodal analgesia acts. This entry is also the
  conformance home for the preclinical `spinal_hsp90_opioid_enhancement` module:
  the flagship study of that module (Bowden et al. 2026, PMID:41031962) tested the
  rat/mouse paw-incision (Brennan) model, the standard preclinical analogue of
  acute post-surgical pain.

  Publication review in 2026 expanded the original targeted-literature curation
  with contemporary prevalence and risk-factor evidence, functional pain
  assessment, regional analgesia guidance, and the pivotal postoperative trials
  of suzetrigine. The entry remains mechanism-first rather than a prescriptive
  peri-operative care protocol, consistent with DisMech scope.
pathophysiology:
- name: Surgical Incision and Nociceptor Activation
  description: >-
    The trigger. A surgical incision through skin, fascia, and muscle directly
    activates high-threshold A-delta and C-fiber nociceptors at the wound. In the
    Brennan rat plantar-incision model - the standard preclinical analogue of
    human post-surgical pain - a hindpaw incision produces reliable, quantifiable
    mechanical hyperalgesia lasting several days, with input carried by the sural
    and tibial nerves.
  role: trigger
  biological_scale: TISSUE
  cell_types:
  - preferred_term: Nociceptor (A-delta / C-fiber primary afferent)
    term:
      id: CL:0000198
      label: pain receptor cell
  locations:
  - preferred_term: Skin and soft tissue at the surgical wound
    term:
      id: UBERON:0002097
      label: skin of body
  evidence:
  - reference: PMID:8783314
    reference_title: Characterization of a rat model of incisional pain.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      a surgical incision of the rat foot causes a reliable and quantifiable
      mechanical hyperalgesia lasting for several days after surgery
    explanation: >-
      Establishes the trigger: surgical incision produces quantifiable mechanical
      hyperalgesia. Evidence source is MODEL_ORGANISM because this is the Brennan
      rat plantar-incision model, the standard preclinical analogue of acute
      post-surgical pain.
  - reference: PMID:8783314
    reference_title: Characterization of a rat model of incisional pain.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      This model should allow us to understand mechanisms of sensitization caused
      by surgery and investigate new therapies for postoperative pain in humans.
    explanation: >-
      The authors frame the incision model as the tool for studying surgery-caused
      sensitization and testing postoperative-pain therapies, motivating its use
      throughout this entry.
  downstream:
  - target: Inflammatory Mediator Release at the Wound
  - target: Acute post-surgical pain
- name: Inflammatory Mediator Release at the Wound
  description: >-
    The molecular amplifier. Incised and injured tissue and infiltrating immune
    cells release an inflammatory milieu (prostaglandins, bradykinin, protons,
    ATP, cytokines, and nerve growth factor). Receptors, mediators, and
    neurotransmitters driving sensitization after incision have been specifically
    characterized and are in part unique to incisional pain.
  role: amplifier
  biological_scale: MOLECULAR
  locations:
  - preferred_term: Skin and soft tissue at the surgical wound
    term:
      id: UBERON:0002097
      label: skin of body
  evidence:
  - reference: PMID:29392204
    reference_title: Postoperative pain-from mechanisms to treatment.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      the role of certain receptors, mediators, and neurotransmitters involved in
      peripheral and central sensitization after incision were identified
    explanation: >-
      Supports characterized inflammatory mediators/receptors driving
      sensitization after incision. Evidence source is MODEL_ORGANISM because the
      snippet reports findings from rodent incision-model studies.
  downstream:
  - target: Peripheral Nociceptor Sensitization
- name: Peripheral Nociceptor Sensitization
  description: >-
    The cellular amplifier. The inflammatory milieu lowers nociceptor activation
    threshold and raises excitability, producing primary hyperalgesia at and
    immediately around the wound. In the incision model, distinct areas around the
    wound show altered withdrawal thresholds reflecting this peripheral
    sensitization.
  role: amplifier
  biological_scale: CELLULAR
  cell_types:
  - preferred_term: Sensitized nociceptor (A-delta / C-fiber primary afferent)
    term:
      id: CL:0000198
      label: pain receptor cell
  locations:
  - preferred_term: Skin and soft tissue at the surgical wound
    term:
      id: UBERON:0002097
      label: skin of body
  evidence:
  - reference: PMID:8783314
    reference_title: Characterization of a rat model of incisional pain.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      Distinct areas around the wound had different withdrawal thresholds during
      the study period.
    explanation: >-
      Documents spatially graded threshold changes around the incision consistent
      with peripheral nociceptor sensitization. Evidence source MODEL_ORGANISM
      (Brennan rat incision model).
  downstream:
  - target: NaV1.8-Mediated Peripheral Nociceptive Signal Propagation
- name: NaV1.8-Mediated Peripheral Nociceptive Signal Propagation
  description: >-
    NaV1.8 voltage-gated sodium channels on peripheral pain-sensing neurons and
    dorsal-root-ganglion nociceptors sustain action-potential firing and transmit
    incisional pain signals toward the spinal cord. Human-neuron pharmacology
    identifies this peripheral signaling step as a tractable, non-opioid
    therapeutic target.
  role: signal_transmission
  biological_scale: CELLULAR
  cell_types:
  - preferred_term: Peripheral nociceptor
    term:
      id: CL:0000198
      label: pain receptor cell
  molecular_functions:
  - preferred_term: NaV1.8 voltage-gated sodium channel activity
    term:
      id: GO:0005248
      label: voltage-gated sodium channel activity
  evidence:
  - reference: PMID:39775738
    reference_title: "Pharmacology and Mechanism of Action of Suzetrigine, a Potent and Selective Na(V)1.8 Pain Signal Inhibitor for the Treatment of Moderate to Severe Pain."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      This novel allosteric mechanism results in tonic inhibition of NaV1.8 and
      reduces pain signals in primary human DRG sensory neurons.
    explanation: >-
      Human dorsal-root-ganglion neuron electrophysiology directly supports
      NaV1.8-dependent peripheral pain-signal propagation and its inhibition by
      suzetrigine. The evidence source is IN_VITRO because the quoted experiment
      used primary human sensory neurons outside an intact organism.
  downstream:
  - target: Spinal Central Sensitization
- name: Spinal Central Sensitization
  description: >-
    The central effector. Sustained nociceptor barrage into the spinal dorsal
    horn triggers activity-dependent synaptic plasticity - a prolonged, reversible
    increase in the excitability and synaptic efficacy of central nociceptive
    neurons (central sensitization), with a major NMDA-receptor/glutamatergic
    component ("wind-up") and a contribution from activated dorsal-horn microglia.
    Clinically it manifests as pain hypersensitivity beyond the wound: dynamic
    tactile allodynia and secondary hyperalgesia. Post-surgical pain is one of the
    conditions in which central sensitization is an established contributor.
  role: central_effector
  biological_scale: CELLULAR
  cell_types:
  - preferred_term: Spinal dorsal horn microglia
    term:
      id: CL:0000129
      label: microglial cell
  biological_processes:
  - preferred_term: Activity-dependent synaptic potentiation (central sensitization)
    term:
      id: GO:0060291
      label: long-term synaptic potentiation
    modifier: INCREASED
  - preferred_term: NMDA/glutamatergic signaling in the dorsal horn
    term:
      id: GO:0007215
      label: glutamate receptor signaling pathway
    modifier: INCREASED
  - preferred_term: Dorsal-horn microglial activation
    term:
      id: GO:0001774
      label: microglial cell activation
    modifier: INCREASED
  locations:
  - preferred_term: Spinal cord dorsal horn
    term:
      id: UBERON:0002256
      label: dorsal horn of spinal cord
  evidence:
  - reference: PMID:20961685
    reference_title: "Central sensitization: implications for the diagnosis and treatment of pain."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Nociceptor inputs can trigger a prolonged but reversible increase in the
      excitability and synaptic efficacy of neurons in central nociceptive
      pathways, the phenomenon of central sensitization.
    explanation: >-
      Defines central sensitization as nociceptor-input-driven amplification in
      central pathways. Evidence source HUMAN_CLINICAL because the review grounds
      central sensitization in human volunteer studies and clinical cohorts.
  - reference: PMID:20961685
    reference_title: "Central sensitization: implications for the diagnosis and treatment of pain."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Central sensitization manifests as pain hypersensitivity, particularly
      dynamic tactile allodynia, secondary punctate or pressure hyperalgesia
    explanation: >-
      Links central sensitization to allodynia and secondary hyperalgesia, the
      spread of pain beyond the wound seen after surgery.
  - reference: PMID:29392204
    reference_title: Postoperative pain-from mechanisms to treatment.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      Preclinical studies in rodent models characterized responses of primary
      afferent nociceptors and dorsal horn neurons as one neural basis for pain
      behavior
    explanation: >-
      Identifies dorsal-horn neuron responses as a neural basis of postoperative
      pain behavior. Evidence source MODEL_ORGANISM because the snippet reports
      rodent incision-model findings.
  downstream:
  - target: Spinal Microglial Gating of Opioid Antinociception
  - target: Resolution with Wound Healing
  - target: Transition to Chronic Post-Surgical Pain
  - target: Allodynia and secondary hyperalgesia
- name: Spinal Microglial Gating of Opioid Antinociception
  description: >-
    A preclinical therapeutic vulnerability at the same spinal dorsal-horn /
    microglial substrate as the central-sensitization node (its inbound edge). In
    the paw-incision (post-surgical) pain model, spinal Hsp90 inhibition activates
    microglial Src kinase signaling that enhances mu-opioid-receptor
    antinociception, enabling an opioid dose-reduction strategy; better acute
    analgesia via this route is hypothesized to blunt the acute-to-chronic
    transition (its downstream edge). This node conforms to the
    `spinal_hsp90_opioid_enhancement` module. IMPORTANT: the evidence is
    preclinical (mouse, intrathecal/isoform-selective dosing) and
    spinal-compartment-specific - brain/systemic non-selective Hsp90 inhibition
    blocks opioid antinociception - so this is a research target, not established
    human therapy.
  role: therapeutic_vulnerability
  biological_scale: CELLULAR
  conforms_to: "spinal_hsp90_opioid_enhancement#Microglial Src Kinase Activation"
  cell_types:
  - preferred_term: Spinal dorsal horn microglia
    term:
      id: CL:0000129
      label: microglial cell
  biological_processes:
  - preferred_term: Microglial modulation of spinal opioid antinociceptive signaling
    term:
      id: GO:0038003
      label: G protein-coupled opioid receptor signaling pathway
    modifier: INCREASED
  locations:
  - preferred_term: Spinal cord dorsal horn
    term:
      id: UBERON:0002256
      label: dorsal horn of spinal cord
  evidence:
  - reference: PMID:41031962
    reference_title: Hsp90 inhibition in mouse spinal cord enhances Src kinase signaling in microglia to increase opioid antinociception.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      The enhanced antinociception seen with 17-AAG was completely abolished in
      the inhibitor groups in tail-flick and paw-incision pain models
    explanation: >-
      Ties the module's opioid-enhancement mechanism directly to the paw-incision
      (post-surgical) pain model. Evidence source is MODEL_ORGANISM (mouse).
  - reference: PMID:41031962
    reference_title: Hsp90 inhibition in mouse spinal cord enhances Src kinase signaling in microglia to increase opioid antinociception.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      colocalization of activated Src with microglia
    explanation: >-
      Localizes the enhancing Src signaling to microglia, the cellular substrate
      of this therapeutic-vulnerability node and the module conformance target.
  downstream:
  - target: Transition to Chronic Post-Surgical Pain
- name: Resolution with Wound Healing
  description: >-
    The expected consequence. In most patients the sensitized state resolves as
    the surgical wound heals over days to weeks; only a minority progress to
    persistent pain.
  role: consequence
  biological_scale: ORGANISM
  evidence:
  - reference: PMID:16698416
    reference_title: "Persistent postsurgical pain: risk factors and prevention."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Acute postoperative pain is followed by persistent pain in 10-50% of
      individuals after common operations
    explanation: >-
      The reported minority progressing to persistent pain implies that most
      patients do not develop chronic pain, but the quoted text does not directly
      establish wound healing as the mechanism of resolution; polarity is
      therefore PARTIAL.
- name: Transition to Chronic Post-Surgical Pain
  description: >-
    The adverse consequence. In a substantial minority the sensitized state
    persists as chronic post-surgical pain (CPSP) - reported in 10-50% of
    individuals after common operations, severe in ~2-10% - often with a
    neuropathic component from intraoperative nerve injury. The intensity of the
    acute pain is a key predictor of this transition, the rationale for
    aggressive, opioid-sparing acute pain control.
  role: consequence
  biological_scale: ORGANISM
  evidence:
  - reference: PMID:16698416
    reference_title: "Persistent postsurgical pain: risk factors and prevention."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Acute postoperative pain is followed by persistent pain in 10-50% of
      individuals after common operations, such as groin hernia repair, breast and
      thoracic surgery, leg amputation, and coronary artery bypass surgery.
    explanation: >-
      Quantifies the acute-to-chronic transition across common operations.
      Evidence source HUMAN_CLINICAL (human epidemiology in a clinical review).
  - reference: PMID:16698416
    reference_title: "Persistent postsurgical pain: risk factors and prevention."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      the intensity of acute postoperative pain correlates with the risk of
      developing a persistent pain state
    explanation: >-
      States the central clinical link modeled by this node: acute pain intensity
      predicts CPSP, motivating aggressive acute analgesia.
  - reference: PMID:16698416
    reference_title: "Persistent postsurgical pain: risk factors and prevention."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Iatrogenic neuropathic pain is probably the most important cause of
      long-term postsurgical pain.
    explanation: >-
      Attributes much long-term CPSP to iatrogenic neuropathic injury, the
      neuropathic component noted in this node.
  - reference: PMID:38809229
    reference_title: A prospective cohort study of chronic postsurgical pain after ambulatory surgeries.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Every unit increase in pain over the first 24 h was significantly associated
      with increased odds of moderate-to-severe CPSP at 3 months; odds ratio =
      1.28, 95% CI = 1.04-1.58.
    explanation: >-
      A contemporary prospective ambulatory-surgery cohort quantifies the
      association between early acute pain intensity and moderate-to-severe CPSP.
  downstream:
  - target: Chronic post-surgical pain
phenotypes:
- name: Acute post-surgical pain
  category: Phenotype
  description: >-
    Acute nociceptive pain at and around the surgical wound. Moderate or severe
    pain affects nearly half of adults undergoing surgery despite contemporary
    peri-operative care.
  phenotype_term:
    preferred_term: Pain
    term:
      id: HP:0012531
      label: Pain
    temporality: ACUTE
  evidence:
  - reference: PMID:39319373
    reference_title: "Peri-operative pain management in adults: a multidisciplinary consensus statement from the Association of Anaesthetists and the British Pain Society."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Nearly half of adult patients undergoing surgery experience moderate or
      severe postoperative pain.
    explanation: >-
      Provides a contemporary consensus-review estimate for clinically important
      acute postoperative pain in adults.
- name: Allodynia and secondary hyperalgesia
  category: Phenotype
  description: >-
    Pain from normally non-painful stimuli (tactile allodynia) and heightened pain
    in uninjured tissue surrounding the wound (secondary hyperalgesia), reflecting
    central sensitization.
  phenotype_term:
    preferred_term: Allodynia
    term:
      id: HP:0012533
      label: Allodynia
  evidence:
  - reference: PMID:20961685
    reference_title: "Central sensitization: implications for the diagnosis and treatment of pain."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Central sensitization manifests as pain hypersensitivity, particularly
      dynamic tactile allodynia, secondary punctate or pressure hyperalgesia
    explanation: >-
      Maps allodynia and secondary hyperalgesia to central sensitization.
      Evidence source HUMAN_CLINICAL (human volunteer/cohort grounding in the
      cited review).
- name: Chronic post-surgical pain
  category: Phenotype
  description: >-
    Persistent pain lasting beyond normal healing (>3 months) in a subset of
    surgical patients, often with a neuropathic component.
  phenotype_term:
    preferred_term: Chronic pain
    term:
      id: HP:0012532
      label: Chronic pain
    temporality: CHRONIC
  evidence:
  - reference: PMID:16698416
    reference_title: "Persistent postsurgical pain: risk factors and prevention."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Acute postoperative pain is followed by persistent pain in 10-50% of
      individuals after common operations
    explanation: >-
      Supports chronic post-surgical pain as a sequela in a substantial subset
      (10-50% across common operations). Frequency band omitted because the source
      reports a wide range rather than a single enum-mappable band.
  - reference: PMID:38809229
    reference_title: A prospective cohort study of chronic postsurgical pain after ambulatory surgeries.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      CPSP was defined as chronic pain that developed or increased in intensity
      after the surgical procedure and is localized to the surgical field or
      within the innervation territory of a nerve in the surgical field, and has
      persisted for 3 months post-surgery, with the exclusion of other causes of
      pain.
    explanation: >-
      Supports the three-month duration, surgical-field localization, and
      exclusion-of-other-causes scope of the chronic sequela.
prevalence:
- population: Post-discharge surgical cohorts
  measure_type: PERIOD_PREVALENCE
  prevalence_class: COMMON
  rate_per_100000: 44500.0
  rate_low: 31000.0
  rate_high: 58000.0
  notes: >-
    Conditional prevalence among people who underwent surgery, measured during
    the first 1-14 days after hospital discharge; this is not general-population
    prevalence.
  evidence:
  - reference: PMID:37181639
    reference_title: "Prevalence of postoperative pain after hospital discharge: systematic review and meta-analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Meta-analyses of combinable studies provided estimates of pooled prevalence
      rates of moderate-to-severe postoperative pain ranging from 31% 1 day after
      discharge to 58% 1 to 2 weeks after discharge.
    explanation: >-
      Quantifies the common conditional prevalence of moderate-to-severe pain
      after discharge across 27 studies and 22,108 surgical participants.
environmental:
- name: Pre-existing pain and heightened pain sensitivity
  description: >-
    Preoperative pain history and greater pain sensitivity are candidate
    risk-stratification domains for moderate-to-severe acute postsurgical pain.
  presence: Positive
  evidence:
  - reference: PMID:38799277
    reference_title: "Risk Factors for Acute Postsurgical Pain: A Narrative Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      This review investigates the risk factors for APSP, including gender, age,
      obesity, smoking history, preoperative pain history, pain sensitivity,
      preoperative anxiety, depression, pain catastrophizing, expected
      postoperative pain, surgical fear, and genetic polymorphisms.
    explanation: >-
      The narrative review enumerates preoperative pain and pain sensitivity in
      its APSP risk-factor scope, but this abstract sentence does not quantify or
      independently confirm either association; polarity is therefore PARTIAL.
- name: Psychological vulnerability before surgery
  description: >-
    Preoperative anxiety, depression, pain catastrophizing, fear of surgery, and
    high expected postoperative pain are candidate psychological
    risk-stratification domains for acute postsurgical pain.
  presence: Positive
  evidence:
  - reference: PMID:38799277
    reference_title: "Risk Factors for Acute Postsurgical Pain: A Narrative Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      This review investigates the risk factors for APSP, including gender, age,
      obesity, smoking history, preoperative pain history, pain sensitivity,
      preoperative anxiety, depression, pain catastrophizing, expected
      postoperative pain, surgical fear, and genetic polymorphisms.
    explanation: >-
      The narrative review enumerates these psychological variables in its APSP
      risk-factor scope, but this abstract sentence does not quantify or
      independently confirm each association; polarity is therefore PARTIAL.
diagnosis:
- name: Function-guided peri-operative pain assessment
  description: >-
    Repeated pain assessment across the peri-operative pathway should evaluate
    functional interference as well as pain intensity, guiding reassessment of
    analgesia rather than treating a unidimensional score alone.
  diagnosis_term:
    preferred_term: Pain assessment
    term:
      id: NCIT:C20992
      label: Pain Assessment
  results: >-
    Moderate or severe pain and pain that impairs recovery functions indicate
    inadequately controlled postoperative pain and the need to reassess the
    analgesic plan.
  evidence:
  - reference: PMID:39319373
    reference_title: "Peri-operative pain management in adults: a multidisciplinary consensus statement from the Association of Anaesthetists and the British Pain Society."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      assessing pain to facilitate function; use of multimodal analgesia,
      including regional anaesthesia; non-pharmacological strategies; safe use of
      opioids; and use of protocols and training for staff in caring for patients
      with postoperative pain.
    explanation: >-
      The multidisciplinary consensus explicitly makes function-facilitating pain
      assessment a generic principle. Evidence source is OTHER because the claim
      is a Delphi consensus recommendation rather than a patient-level study.
treatments:
- name: Multimodal (Opioid-Sparing) Analgesia
  description: >-
    Combining analgesics and techniques with different mechanisms - non-opioid
    systemics (acetaminophen, NSAIDs/COX-2 inhibitors), regional/neuraxial local
    anesthesia, and adjuncts such as ketamine (modeled separately below) - to
    control acute pain while reducing opioid consumption and side effects and
    enhancing recovery.
  treatment_term:
    preferred_term: Multimodal analgesia (pain management)
    term:
      id: NCIT:C15180
      label: Pain Therapy
  evidence:
  - reference: PMID:29392204
    reference_title: Postoperative pain-from mechanisms to treatment.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Scientific evidence is able to point towards useful (and less useful)
      elements of multimodal analgesia able to reduce opioid consumption, improve
      pain management, and enhance recovery.
    explanation: >-
      Supports multimodal, opioid-sparing analgesia as the evidence-based approach.
      Evidence source HUMAN_CLINICAL (guideline/clinical-evidence synthesis).
  - reference: PMID:39319373
    reference_title: "Peri-operative pain management in adults: a multidisciplinary consensus statement from the Association of Anaesthetists and the British Pain Society."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      use of multimodal analgesia, including regional anaesthesia;
      non-pharmacological strategies; safe use of opioids
    explanation: >-
      A contemporary multidisciplinary consensus endorses multimodal analgesia,
      regional techniques, non-pharmacological strategies, and safe opioid use.
      Evidence source is OTHER because the quoted claim is a Delphi consensus.
- name: Local and Regional Analgesia
  description: >-
    Regional techniques such as fascial-plane blocks can reduce early
    postoperative pain and opioid requirements for selected procedures.
    Technique selection is procedure-specific and requires trained staff and
    safety protocols.
  treatment_term:
    preferred_term: Regional anesthesia procedure
    term:
      id: NCIT:C64381
      label: Regional Anesthesia Procedure
  evidence:
  - reference: PMID:41363869
    reference_title: 2026 American Society of Anesthesiologists Practice Guideline on Perioperative Pain Management Using Local and Regional Analgesia for Cardiothoracic Surgeries, Mastectomy, and Abdominal Surgeries.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      For adults, the American Society of Anesthesiologists (Schaumburg, Illinois)
      Task Force on Perioperative Pain Management strongly recommends fascial
      plane blocks to reduce pain and/or opioid requirements in the first 24 h
      postoperatively for open cardiothoracic, abdominal, retroperitoneal, and
      pelvic surgeries and mastectomy.
    explanation: >-
      The current ASA practice guideline directly supports regional fascial-plane
      blocks for early postoperative pain and opioid reduction. Evidence source is
      OTHER because the quoted statement is a guideline recommendation.
- name: Opioid Analgesic Therapy
  description: >-
    Mu-opioid agonists (e.g., morphine) can be used within multimodal care for
    moderate-to-severe acute post-surgical pain, but their adverse effects and
    persistent-use risk motivate safe-use and opioid-sparing strategies and, in
    preclinical research, opioid adjuvants.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: opioid analgesic agent therapy
    term:
      id: NCIT:C15180
      label: Pain Therapy
    therapeutic_agent:
    - preferred_term: morphine
      term:
        id: CHEBI:17303
        label: morphine
  evidence:
  - reference: PMID:39319373
    reference_title: "Peri-operative pain management in adults: a multidisciplinary consensus statement from the Association of Anaesthetists and the British Pain Society."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      use of multimodal analgesia, including regional anaesthesia;
      non-pharmacological strategies; safe use of opioids
    explanation: >-
      The multidisciplinary consensus explicitly places safe opioid use within a
      multimodal peri-operative pain strategy. Evidence source is OTHER because
      the quoted claim is a Delphi consensus.
- name: NMDA-Antagonist Adjuvant (Ketamine)
  description: >-
    Perioperative low-dose ketamine, an NMDA-receptor antagonist, acts on the
    spinal central-sensitization node (the NMDA/glutamatergic "wind-up"
    component), reducing postoperative pain and opioid consumption and
    contributing preventive analgesia.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: ketamine
      term:
        id: CHEBI:6121
        label: ketamine
  target_mechanisms:
  - target: Spinal Central Sensitization
    treatment_effect: INHIBITS
    description: >-
      NMDA-receptor antagonism dampens the glutamatergic wind-up that drives
      spinal central sensitization, reducing pain and opioid requirement.
  evidence:
  - reference: PMID:15105220
    reference_title: A qualitative systematic review of the role of N-methyl-D-aspartate receptor antagonists in preventive analgesia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Dextromethorphan and ketamine were found to have significant immediate and
      preventive analgesic benefit in 67% and 58% of studies, respectively.
    explanation: >-
      Supports ketamine (NMDA antagonist) reducing postoperative pain/analgesic
      consumption. Evidence source HUMAN_CLINICAL (qualitative systematic review
      of perioperative randomized trials).
- name: Suzetrigine (NaV1.8 Inhibitor)
  description: >-
    Suzetrigine is an oral, first-in-class non-opioid analgesic for
    moderate-to-severe acute pain. It selectively inhibits peripheral NaV1.8
    channels; two large phase III postoperative trials after abdominoplasty and
    bunionectomy showed clinically meaningful pain reduction versus placebo and
    pain reduction similar to hydrocodone/acetaminophen over 48 hours.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: suzetrigine
      term:
        id: NCIT:C199115
        label: Suzetrigine
  target_mechanisms:
  - target: NaV1.8-Mediated Peripheral Nociceptive Signal Propagation
    treatment_effect: INHIBITS
    description: >-
      Selective NaV1.8 inhibition reduces action-potential firing and pain-signal
      transmission in peripheral human dorsal-root-ganglion sensory neurons.
    evidence:
    - reference: PMID:39775738
      reference_title: "Pharmacology and Mechanism of Action of Suzetrigine, a Potent and Selective Na(V)1.8 Pain Signal Inhibitor for the Treatment of Moderate to Severe Pain."
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: >-
        This novel allosteric mechanism results in tonic inhibition of NaV1.8 and
        reduces pain signals in primary human DRG sensory neurons.
      explanation: >-
        Human sensory-neuron electrophysiology directly supports the modeled
        mechanism target and inhibitory treatment effect.
  evidence:
  - reference: PMID:40117446
    reference_title: "Suzetrigine, a Nonopioid Na V 1.8 Inhibitor for Treatment of Moderate-to-severe Acute Pain: Two Phase 3 Randomized Clinical Trials."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      As compared with placebo, suzetrigine reduced moderate-to-severe acute pain
      over 48 h after abdominoplasty or bunionectomy. Pain reduction with
      suzetrigine was similar to that with hydrocodone bitartrate/acetaminophen.
    explanation: >-
      Two randomized, placebo- and active-controlled phase III postoperative-pain
      trials directly support clinical efficacy and appropriately limit the claim
      to the studied procedures and 48-hour endpoint.
- name: Spinal-Selective Hsp90 Inhibitor (Preclinical Opioid Adjuvant)
  description: >-
    A preclinical opioid-adjuvant strategy: spinal-cord-directed Hsp90 inhibition
    (intrathecal 17-AAG/tanespimycin, or spinal-selective Hsp90-beta/Grp94
    inhibitors) enhances mu-opioid antinociception in the paw-incision
    (post-surgical) pain model via microglial Src signaling, enabling opioid dose
    reduction and tolerance rescue. NOT an established human therapy - effect is
    spinal-compartment-specific and demonstrated only in rodents.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: 17-AAG (tanespimycin)
      term:
        id: CHEBI:64153
        label: tanespimycin
  target_mechanisms:
  - target: Spinal Microglial Gating of Opioid Antinociception
    treatment_effect: ACTIVATES
    description: >-
      Spinal Hsp90 inhibition activates the microglial Src signaling that gates
      enhanced opioid antinociception, potentiating analgesia and rescuing
      tolerance in the paw-incision model (conforms to the
      spinal_hsp90_opioid_enhancement module).
  evidence:
  - reference: PMID:41031962
    reference_title: Hsp90 inhibition in mouse spinal cord enhances Src kinase signaling in microglia to increase opioid antinociception.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      The enhanced antinociception seen with 17-AAG was completely abolished in
      the inhibitor groups in tail-flick and paw-incision pain models
    explanation: >-
      Supports the adjuvant mechanism specifically in the paw-incision
      (post-surgical) model. Evidence source MODEL_ORGANISM (mouse); this is a
      preclinical research target, not established therapy.
clinical_trials:
- name: NCT05558410
  phase: PHASE_III
  status: COMPLETED
  description: >-
    Randomized, double-blind, placebo-controlled pivotal trial of suzetrigine for
    moderate-to-severe acute pain after abdominoplasty.
  target_phenotypes:
  - preferred_term: Acute pain
    term:
      id: HP:0012531
      label: Pain
    temporality: ACUTE
  evidence:
  - reference: clinicaltrials:NCT05558410
    reference_title: A Phase 3, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Suzetrigine for Acute Pain After an Abdominoplasty
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The purpose of this study was to evaluate the efficacy and safety of
      Suzetrigine (SUZ) in treating acute pain after an abdominoplasty.
    explanation: >-
      ClinicalTrials.gov identifies this pivotal phase III postoperative-pain
      trial and its disease-relevant intervention and surgical setting.
- name: NCT05553366
  phase: PHASE_III
  status: COMPLETED
  description: >-
    Randomized, double-blind, placebo-controlled pivotal trial of suzetrigine for
    moderate-to-severe acute pain after bunionectomy.
  target_phenotypes:
  - preferred_term: Acute pain
    term:
      id: HP:0012531
      label: Pain
    temporality: ACUTE
  evidence:
  - reference: clinicaltrials:NCT05553366
    reference_title: A Phase 3, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of VX-548 for Acute Pain After a Bunionectomy
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The purpose of this study is to evaluate the efficacy and safety of
      suzetrigine for acute pain after a bunionectomy.
    explanation: >-
      ClinicalTrials.gov identifies this pivotal phase III postoperative-pain
      trial and its disease-relevant intervention and surgical setting.
discussions:
- discussion_id: gap_apsp_hsp90_adjuvant_translation
  prompt: >-
    Can spinal-selective Hsp90 inhibition translate into a human opioid-sparing
    adjuvant for acute post-surgical pain, and does reducing acute pain intensity
    by this route lower the incidence of chronic post-surgical pain?
  kind: KNOWLEDGE_GAP
  status: OPEN
  attaches_to:
  - pathophysiology#Spinal Microglial Gating of Opioid Antinociception
  - pathophysiology#Transition to Chronic Post-Surgical Pain
  rationale: >-
    The Hsp90-adjuvant mechanism is established only in rodent incision models and
    is spinal-compartment-specific. Whether it is achievable and beneficial in
    humans - and whether better acute analgesia via this route reduces CPSP - is
    unknown.
references:
- reference: PMID:8783314
  title: Characterization of a rat model of incisional pain.
- reference: PMID:29392204
  title: Postoperative pain-from mechanisms to treatment.
- reference: PMID:16698416
  title: "Persistent postsurgical pain: risk factors and prevention."
- reference: PMID:20961685
  title: "Central sensitization: implications for the diagnosis and treatment of pain."
- reference: PMID:15105220
  title: A qualitative systematic review of the role of N-methyl-D-aspartate receptor antagonists in preventive analgesia.
- reference: PMID:41031962
  title: Hsp90 inhibition in mouse spinal cord enhances Src kinase signaling in microglia to increase opioid antinociception.
- reference: PMID:37181639
  title: "Prevalence of postoperative pain after hospital discharge: systematic review and meta-analysis."
- reference: PMID:38799277
  title: "Risk Factors for Acute Postsurgical Pain: A Narrative Review."
- reference: PMID:38809229
  title: A prospective cohort study of chronic postsurgical pain after ambulatory surgeries.
- reference: PMID:39319373
  title: "Peri-operative pain management in adults: a multidisciplinary consensus statement from the Association of Anaesthetists and the British Pain Society."
- reference: PMID:39775738
  title: Pharmacology and Mechanism of Action of Suzetrigine, a Potent and Selective Na(V)1.8 Pain Signal Inhibitor for the Treatment of Moderate to Severe Pain.
- reference: PMID:40117446
  title: "Suzetrigine, a Nonopioid Na V 1.8 Inhibitor for Treatment of Moderate-to-severe Acute Pain: Two Phase 3 Randomized Clinical Trials."
- reference: PMID:41363869
  title: 2026 American Society of Anesthesiologists Practice Guideline on Perioperative Pain Management Using Local and Regional Analgesia for Cardiothoracic Surgeries, Mastectomy, and Abdominal Surgeries.
datasets:
- accession: geo:GSE125076
  title: A mouse model of acute post-surgical pain
  description: Pain is the leading cause of disability in the developed world but remains a poorly treated condition. Specifically, post-surgical pain continues to be a frequent and undermanaged condition. Here, we investigate the analgesic potential of pharmacological NaV1.7 inhibition in a mouse model of acute post-surgical pain, based on incision of the plantar skin and underlying muscle of the hind paw. We demonstrate that local and systemic treatment with the selective NaV1.7 inhibitor μ-theraphotoxin-Pn3a is effectively anti-allodynic in this model and completely reverses mechanical hypersensitivity in the absence of motor adverse effects.
  organism:
    preferred_term: mouse
    term:
      id: NCBITaxon:10090
      label: Mus musculus
  data_type: BULK_RNA_SEQ
  sample_count: 6
  publication: PMID:31335646
  notes: Identified by GEO DataSets index search for Acute Post-Surgical Pain (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
- accession: geo:GSE242389
  title: Human birth tissue products as a regenerative medicine for post-surgical pain through multi-modal action
  description: Post-surgical pain causes significant suffering. Extracts of the human amniotic membrane (AM) may be novel regenerative matrices, but little is known about their use in pain treatment. Locally applying FLO (particulates of AM) in mice acutely attenuated post-surgical pain hypersensitivity and inhibited its transition to a prolonged state after plantar-incision. Mechanistically, this was achieved through direct nociceptive neuronal inhibition via CD44-dependent mechanisms and indirect anti-pain effect by attenuating immune cell recruitment and promoting wound healing.
  organism:
    preferred_term: mouse
    term:
      id: NCBITaxon:10090
      label: Mus musculus
  data_type: BULK_RNA_SEQ
  sample_count: 6
  publication: PMID:39594635
  notes: Identified by GEO DataSets index search for Acute Post-Surgical Pain (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
📚

References & Deep Research

References

13
PMID:8783314
Characterization of a rat model of incisional pain.
No top-level findings curated for this source.
PMID:29392204
Postoperative pain-from mechanisms to treatment.
No top-level findings curated for this source.
PMID:16698416
Persistent postsurgical pain: risk factors and prevention.
No top-level findings curated for this source.
PMID:20961685
Central sensitization: implications for the diagnosis and treatment of pain.
No top-level findings curated for this source.
PMID:15105220
A qualitative systematic review of the role of N-methyl-D-aspartate receptor antagonists in preventive analgesia.
No top-level findings curated for this source.
PMID:41031962
Hsp90 inhibition in mouse spinal cord enhances Src kinase signaling in microglia to increase opioid antinociception.
No top-level findings curated for this source.
PMID:37181639
Prevalence of postoperative pain after hospital discharge: systematic review and meta-analysis.
No top-level findings curated for this source.
PMID:38799277
Risk Factors for Acute Postsurgical Pain: A Narrative Review.
No top-level findings curated for this source.
PMID:38809229
A prospective cohort study of chronic postsurgical pain after ambulatory surgeries.
No top-level findings curated for this source.
PMID:39319373
Peri-operative pain management in adults: a multidisciplinary consensus statement from the Association of Anaesthetists and the British Pain Society.
No top-level findings curated for this source.
PMID:39775738
Pharmacology and Mechanism of Action of Suzetrigine, a Potent and Selective Na(V)1.8 Pain Signal Inhibitor for the Treatment of Moderate to Severe Pain.
No top-level findings curated for this source.
PMID:40117446
Suzetrigine, a Nonopioid Na V 1.8 Inhibitor for Treatment of Moderate-to-severe Acute Pain: Two Phase 3 Randomized Clinical Trials.
No top-level findings curated for this source.
PMID:41363869
2026 American Society of Anesthesiologists Practice Guideline on Perioperative Pain Management Using Local and Regional Analgesia for Cardiothoracic Surgeries, Mastectomy, and Abdominal Surgeries.
No top-level findings curated for this source.