Development and expression of neuropathic pain in CB1 knockout mice.
Neuropathic pain is a clinical manifestation characterized by the presence of spontaneous pain, allodynia and hyperalgesia. Here, we have evaluated the involvement of CB1 cannabinoid receptors in the development and expression of neuropathic pain. For this purpose, partial ligation of the sciatic nerve was performed in CB1 cannabinoid receptor knockout mice and their wild-type littermates. The development of mechanical and thermal allodynia, and thermal hyperalgesia was evaluated by using the von Frey filaments, cold-plate and plantar tests, respectively. Pre-surgical tactile and thermal withdrawal thresholds were similar in both genotypes. In wild-type mice, sciatic nerve injury led to a neuropathic pain syndrome characterized by a marked and long-lasting reduction of the paw withdrawal thresholds to mechanical and thermal stimuli. These manifestations developed similarly in mice lacking CB1 cannabinoid receptors. We have also investigated the consequences of gabapentin administration in these animals. Gabapentin (50 mg/kg/day, i.p.) induced a similar suppression of mechanical and thermal allodynia in both wild-type and CB1 knockout mice. Mild differences between genotypes were observed concerning the effect of gabapentin in the expression of thermal hyperalgesia. Taken together, our results indicate that CB1 cannabinoid receptors are not critically implicated in the development of neuropathic pain nor in the anti-allodynic and anti-hyperalgesic effects of gabapentin in this model.
Castañé
Anna
A
Laboratori de Neurofarmacologia, Facultat de Ciències de la Salut i de la Vida, Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.
Célérier
Evelyne
E
Martín
Miquel
M
Ledent
Catherine
C
Parmentier
Marc
M
Maldonado
Rafael
R
Valverde
Olga
O
D000588:Amines / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology; D000077206:Gabapentin; D006257:Head; D006930:Hyperalgesia / Q000139:chemically induced / Q000523:psychology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010146:Pain / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology*; D010147:Pain Measurement / Q000187:drug effects; D010523:Peripheral Nervous System Diseases / Q000150:complications / Q000235:genetics* / Q000503:physiopathology*; D010812:Physical Stimulation; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics* / Q000502:physiology*; D020426:Sciatic Neuropathy / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D043884:Receptor, Cannabinoid, CB1; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin