The synthetic cannabinoids attenuate allodynia and hyperalgesia in a rat model of trigeminal neuropathic pain
Abstract
Trigeminal neuralgia is a disorder of paroxysmal and severely disabling facial pain and continues to be a real therapeutic challenge. At present there are few effective drugs. Here we have evaluated the effects of the synthetic cannabinoid WIN 55,212-2 on mechanical allodynia and thermal hyperalgesia in a rat model of trigeminal neuropathic pain produced by a chronic constriction injury (CCI) of the infraorbital branch of the trigeminal nerve (ION). Relative to sham operation controls, rats with the CCI-ION consistently displayed hyperresponsiveness to von Frey filament and heat stimulation of the vibrissal pad. Both mechanical allodynia and thermal hyperalgesia are seen both ipsilateral and contralateral to the side of nerve injury, but is significantly more severe ipsilaterally. Administration of WIN 55,212-2 (0.3-5 mg/kg i.p.) dose-dependently increased the mechanical and heat withdrawal thresholds. WIN 55,212-2 (0.3-3 mg/kg i.p.) produced no significant motor deficits in animals using the rotarod test. The effect of WIN 55,212-2 was mimicked by cannabinoid CB1 receptor agonist HU 210 and was antagonized by CB1 receptor antagonist AM 251, but not by CB2 receptor antagonist AM 630 or vanilloid receptor 1 antagonist capsazepine, suggesting the involvement of CB1 receptors. CCI-ION also induced a time-dependent upregulation of CB1 receptors primarily within the ipsilateral superficial laminae of the trigeminal caudal nucleus revealed by both Western blot and immunohistochemistry. Taken together, these results suggest that cannabinoids may be a useful therapeutic approach for the clinical management of trigeminal neuropathic pain disorders.
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High antihyperalgesic doses of WIN55,212-2 decreased rotarod latencies and body temperature, whereas HU210 at the low dose used had no effect on these dependent measures.
“High antihyperalgesic doses of WIN55,212-2 decreased rotarod latencies and body temperature, whereas HU210, at the singular low dose used (10 μg/kg), had no effect on these dependent measures.”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [94]
WIN55,212-2 and HU-210 increased mechanical withdrawal responses and thermal withdrawal latencies on the ipsilateral side of the head in the CCI-ION model.
“WIN55,212-2 and HU-210 increased mechanical withdrawal responses and thermal withdrawal latencies on the ipsilateral side of the head in this model.94”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [94]
WIN55,212-2 was more efficacious in suppressing mechanical allodynia vs. thermal hyperalgesia in the CCI-ION model.
“WIN55,212-2 was more efficacious in suppressing mechanical allodynia vs. thermal hyperalgesia in the CCI-ION model.”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [94]
CB1 receptor upregulation was observed in both the ipsilateral and contralateral superficial layer of the trigeminal caudal nucleus, and this effect was greater on the ipsilateral side.
“CB1 receptor upregulation was observed in both the ipsilateral and contralateral superficial layer of the trigeminal caudal nucleus, and this effect was greater on the ipsilateral side.”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [94]
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Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside
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“The doses for WIN2, AM251 and AM630 were chosen based on effective doses in similar studies by others [19,32].”
Method
- Authors
- Liang, Y.-C., Huang, C.-C., & Hsu, K.-S.
- Affiliations
- National Cheng Kung University (TW)
- Corresponding author
- Hsu, Kuei-Sen
- ORCID
- Hsu, Kuei-Sen
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2007-07
- Volume
- 53
- Issue
- 1
- Pages
- 169-177
- ISSN
- 0028-3908 (ISSN-L)
- OpenAlex
- W2092496616
- Cited by
- 68
- References
- 40
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 6 · 2023: 3 · 2022: 7 · 2021: 6 · 2020: 4 · 2019: 3 · 2018: 5 · 2017: 3 · 2016: 3 · 2015: 2 · 2014: 4 · 2013: 3 · 2012: 7
- FWCI
- 2.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Council
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
- Keywords
- synthetic cannabinoids, WIN 55,212-2, trigeminal neuropathic pain, trigeminal neuralgia, chronic constriction injury, infraorbital nerve, mechanical allodynia, thermal hyperalgesia, CB1 receptor, HU-210, AM251, capsazepine, cannabinoid therapy
- MeSH terms
- Analgesics, Analysis of Variance, Animals, Cannabinoids, Disease Models, Animal, Dose-Response Relationship, Drug, Hyperalgesia, Hyperesthesia, Indoles, Functional Laterality, Male, Morpholines, Naphthalenes, Pain Measurement, Piperidines, Pyrazoles, Reaction Time, Time Factors, Rats, Sprague-Dawley, Pain Threshold, Trigeminal Nerve Diseases, Receptor, Cannabinoid, CB1, Benzoxazines, Rats
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