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Cannabinoid subtype-2 receptors modulate the antihyperalgesic effect of WIN 55,212-2 in rats with neuropathic spinal cord injury pain.
Spine J. 2010 Dec; 10(12):1049-54.SJ

Abstract

BACKGROUND CONTEXT

There is increasing evidence for a role of the cannabinoid (CB) system in the development of neuropathic pain (NP) after spinal cord injury (SCI). The nonspecific CB₁ and CB₂ receptor agonists, WIN 55, 212-2 (WIN), have previously been shown to alleviate both mechanical and thermal hyperalgesia (TH) after peripheral nerve injury.

PURPOSE

The present study was designed to identify the CB receptors involved in the antihyperalgesic effect of WIN by using selective antagonists for CB₁ and CB₂ receptors.

STUDY DESIGN

This is an in vivo and behavioral study using a moderate T9 contusion SCI. After injury, TH of the hind paws was measured on postinjury days 21 through 42.

METHODS

Sprague-Dawley rats underwent a contusion SCI using the Multicenter Animal Spinal Cord Injury Study (MASCIS) weight-drop impactor, which induced a moderate T9 SCI. Only animals showing consistent plantar stepping and consistent forelimb and hind limb coordination (Basso, Beattie, and Bresnahan score=15) were tested for TH. Animals exhibiting decreased withdrawal latency time, indicating TH, on or before Day 42, were selected for pharmacological intervention. Animals not exhibiting TH did not receive pharmacological intervention and were sacrificed. Rats underwent hind paw testing before any drug administration (after injury), 45 minutes after selective CB antagonist (AM 251 or AM 630) administration (postantagonist) and again 45 minutes after WIN administration (post-WIN). There were a total of seven treatment groups: saline vehicle control; Dimethyl sulfoxide (DMSO) vehicle control; low-dose WIN (0.2 mg/kg); and high-dose WIN (2.0 mg/kg); AM 251 (3 mg/kg) and AM 630 (1 mg/kg) were given subcutaneously in a total volume of 0.5 mL. Followed by intraperitoneal injection of WIN after each antagonist, sham-operated rats repeated pharmacological intervention used with treatment Groups 5 and 6.

RESULTS

Thermal hyperalgesia was significantly ameliorated in a dose-dependent manner with systemically administered WIN. Cannabinoid receptor Type 1 antagonist AM 251 pretreatment did not affect the antihyperalgesic effect of WIN. By contrast, pretreatment with the CB₂ receptor antagonist AM 630 significantly attenuated the effect of WIN.

CONCLUSION

Taken together, these results suggest a role of the CB₂ receptor in modulating SCI-induced TH. Selective activation of the CB₂ receptor could potentially lead to analgesic effects on NP while avoiding psychotropic side effects in patients with SCI.

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Authors+Show Affiliations

Ahmed MM
Department of Neurological Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
Rajpal S
No affiliation info available
Sweeney C
No affiliation info available
Gerovac TA
No affiliation info available
Allcock B
No affiliation info available
McChesney S
No affiliation info available
Patel AU
No affiliation info available
Tilghman JI
No affiliation info available
Miranpuri GS
No affiliation info available
Resnick DK
No affiliation info available

MeSH

AnalgesicsAnalysis of VarianceAnimalsBenzoxazinesDose-Response Relationship, DrugHot TemperatureHyperalgesiaMaleMorpholinesNaphthalenesNeuralgiaPain MeasurementPiperidinesPyrazolesRatsRats, Sprague-DawleyReceptor, Cannabinoid, CB2Spinal Cord Injuries

Pub Type(s)

Journal Article

Language

eng

PubMed ID

20920894

Citation

Ahmed, Mostafa M., et al. "Cannabinoid Subtype-2 Receptors Modulate the Antihyperalgesic Effect of WIN 55,212-2 in Rats With Neuropathic Spinal Cord Injury Pain." The Spine Journal : Official Journal of the North American Spine Society, vol. 10, no. 12, 2010, pp. 1049-54.
Ahmed MM, Rajpal S, Sweeney C, et al. Cannabinoid subtype-2 receptors modulate the antihyperalgesic effect of WIN 55,212-2 in rats with neuropathic spinal cord injury pain. Spine J. 2010;10(12):1049-54.
Ahmed, M. M., Rajpal, S., Sweeney, C., Gerovac, T. A., Allcock, B., McChesney, S., Patel, A. U., Tilghman, J. I., Miranpuri, G. S., & Resnick, D. K. (2010). Cannabinoid subtype-2 receptors modulate the antihyperalgesic effect of WIN 55,212-2 in rats with neuropathic spinal cord injury pain. The Spine Journal : Official Journal of the North American Spine Society, 10(12), 1049-54. https://doi.org/10.1016/j.spinee.2010.08.015
Ahmed MM, et al. Cannabinoid Subtype-2 Receptors Modulate the Antihyperalgesic Effect of WIN 55,212-2 in Rats With Neuropathic Spinal Cord Injury Pain. Spine J. 2010;10(12):1049-54. PubMed PMID: 20920894.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cannabinoid subtype-2 receptors modulate the antihyperalgesic effect of WIN 55,212-2 in rats with neuropathic spinal cord injury pain. AU - Ahmed,Mostafa M, AU - Rajpal,Sharad, AU - Sweeney,Clayton, AU - Gerovac,Tiffany A, AU - Allcock,Bradley, AU - McChesney,Shannon, AU - Patel,Ami U, AU - Tilghman,Jessica I, AU - Miranpuri,Gurwattan S, AU - Resnick,Daniel K, PY - 2010/01/13/received PY - 2010/06/22/revised PY - 2010/08/22/accepted PY - 2010/10/6/entrez PY - 2010/10/6/pubmed PY - 2011/3/8/medline SP - 1049 EP - 54 JF - The spine journal : official journal of the North American Spine Society JO - Spine J VL - 10 IS - 12 N2 - BACKGROUND CONTEXT: There is increasing evidence for a role of the cannabinoid (CB) system in the development of neuropathic pain (NP) after spinal cord injury (SCI). The nonspecific CB₁ and CB₂ receptor agonists, WIN 55, 212-2 (WIN), have previously been shown to alleviate both mechanical and thermal hyperalgesia (TH) after peripheral nerve injury. PURPOSE: The present study was designed to identify the CB receptors involved in the antihyperalgesic effect of WIN by using selective antagonists for CB₁ and CB₂ receptors. STUDY DESIGN: This is an in vivo and behavioral study using a moderate T9 contusion SCI. After injury, TH of the hind paws was measured on postinjury days 21 through 42. METHODS: Sprague-Dawley rats underwent a contusion SCI using the Multicenter Animal Spinal Cord Injury Study (MASCIS) weight-drop impactor, which induced a moderate T9 SCI. Only animals showing consistent plantar stepping and consistent forelimb and hind limb coordination (Basso, Beattie, and Bresnahan score=15) were tested for TH. Animals exhibiting decreased withdrawal latency time, indicating TH, on or before Day 42, were selected for pharmacological intervention. Animals not exhibiting TH did not receive pharmacological intervention and were sacrificed. Rats underwent hind paw testing before any drug administration (after injury), 45 minutes after selective CB antagonist (AM 251 or AM 630) administration (postantagonist) and again 45 minutes after WIN administration (post-WIN). There were a total of seven treatment groups: saline vehicle control; Dimethyl sulfoxide (DMSO) vehicle control; low-dose WIN (0.2 mg/kg); and high-dose WIN (2.0 mg/kg); AM 251 (3 mg/kg) and AM 630 (1 mg/kg) were given subcutaneously in a total volume of 0.5 mL. Followed by intraperitoneal injection of WIN after each antagonist, sham-operated rats repeated pharmacological intervention used with treatment Groups 5 and 6. RESULTS: Thermal hyperalgesia was significantly ameliorated in a dose-dependent manner with systemically administered WIN. Cannabinoid receptor Type 1 antagonist AM 251 pretreatment did not affect the antihyperalgesic effect of WIN. By contrast, pretreatment with the CB₂ receptor antagonist AM 630 significantly attenuated the effect of WIN. CONCLUSION: Taken together, these results suggest a role of the CB₂ receptor in modulating SCI-induced TH. Selective activation of the CB₂ receptor could potentially lead to analgesic effects on NP while avoiding psychotropic side effects in patients with SCI. SN - 1878-1632 UR - https://www.unboundmedicine.com/medline/citation/20920894/Cannabinoid_subtype_2_receptors_modulate_the_antihyperalgesic_effect_of_WIN_55212_2_in_rats_with_neuropathic_spinal_cord_injury_pain_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1529-9430(10)01110-1 DB - PRIME DP - Unbound Medicine ER -