Differential analgesic sensitivity of two distinct neuropathic pain models
Abstract
In Brief Progressive tactile hypersensitivity (PTH) manifesting after sciatic nerve crush and spared nerve injury (SNI) are two distinct rodent experimental models of neuropathic pain. PTH develops months after recovery from the nerve crush in response to repeated intermittent low-threshold mechanical stimulation of the reinnervated sciatic nerve skin territory and represents a model of stimulus-induced pain. SNI is characterized by an early and sustained increase in stimulus-evoked pain sensitivity in the intact skin territory of the spared sural nerve after sectioning of the two other terminal branches of the sciatic nerve. We examined the effects of morphine (0.5–10 mg/kg), gabapentin (30–200 mg/kg), MK801 (0.01–0.02 mg/kg), amitriptyline (10–25 mg/kg), and carbamazepine (5–7.5 mg/kg) in both models. Morphine, gabapentin, and carbamazepine both reversed and prevented stimulus-induced PTH, whereas MK801 and amitriptyline reduced but did not prevent stimulus-induced PTH. In contrast, the stimulus-evoked behavioral hypersensitivity in the SNI model was poorly modified by these drugs. Independent neuropathic pain models show differential sensitivity to analgesic drug treatment. We suggest that this is due to the different mechanisms responsible for the neuropathic pain-related behavior. Multiple models are required, therefore, to study the mechanisms that contribute to neuropathic pain and to predict analgesic efficacy for different components of the neuropathic pain syndrome. IMPLICATIONS: Analgesic effects of drugs often used for the treatment of neuropathic pain were evaluated in two independent animal models of neuropathic pain. The differential analgesic response between models suggests that different mechanisms are involved and that multiple models are required to study mechanisms and predict drug efficacy for neuropathic pain.
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Standard analgesics (morphine, gabapentin, amitryptiline) are efficacious in treating neuropathic nociception resulting from a crush injury of the sciatic nerve, but showed limited efficacy following SNI.
“Standard analgesics (e.g. morphine, gabapentin, amitryptiline) are efficacious in treating neuropathic nociception resulting from a crush injury of the sciatic nerve, but showed limited efficacy following SNI.101”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [101]
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Serafini, R. A., Giotti, B., Luebbers, A., Pryce, K. D., Giosan, I. M., Tuffy, M. J., Zimering, J. H., Ramakrishnan, A., Lee, D., Kintsurashvili, E., et al. (2026) · Science Signaling · doi:10.1126/scisignal.aed7175
- Authors
- Decosterd, I., Allchorne, A., & Woolf, C. J.
- Affiliations
- Harvard University (US)
- ORCID
- Woolf, Clifford J.
- Venue
- Anesthesia & Analgesia
- Published
- 2004-08
- Volume
- 99
- Issue
- 2
- Pages
- 457-463
- ISSN
- 0003-2999 (ISSN-L)
- OpenAlex
- W2026527037
- Cited by
- 82
- References
- 25
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 3 · 2017: 2 · 2016: 3 · 2015: 4 · 2014: 3 · 2013: 2 · 2012: 4
- FWCI
- 6.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Anesthesia & Analgesia (publishedVersion)
- PubMed (publishedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- neuropathic pain, spared nerve injury, sciatic nerve crush injury, morphine, gabapentin, carbamazepine, amitriptyline, MK-801, tactile hypersensitivity, analgesic sensitivity
- MeSH terms
- Gabapentin, Acetates, Amines, Analgesics, Analgesics, Opioid, Animals, Cold Temperature, Cyclohexanecarboxylic Acids, Disease Models, Animal, gamma-Aminobutyric Acid, Hot Temperature, Hyperalgesia, Male, Morphine, Nerve Crush, Pain, Pain Measurement, Peripheral Nervous System Diseases, Physical Stimulation, Dizocilpine Maleate, Rats, Sprague-Dawley, Neuroprotective Agents, Sciatic Neuropathy, Rats
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