Gabapentin reverses mechanical allodynia induced by sciatic nerve ischemia and formalin-induced nociception in mice.
The anticonvulsant drug gabapentin has been demonstrated to alleviate symptoms of painful diabetic neuropathy as well as other types of neuropathic pain. The aim of the present study was to investigate the effect of gabapentin in a recently developed mouse model of peripheral neuropathy. This model is based on a photochemical ischemic lesion of the sciatic nerve generated by laser-induced activation of the photosensitizing dye erythrosin B. Following laser irradiation of the sciatic nerve for 2, 5, or 10 min, tactile allodynia was observed during at least 3 weeks. The degree of allodynia was most marked following 10 min of irradiation. Subcutaneous administration of gabapentin [175-300 micromol/kg ( approximately 30-51 mg/kg), cumulative doses, at 1-h intervals] significantly reversed tactile allodynia induced by 10-min laser irradiation. The maximal dose of gabapentin increased the withdrawal threshold from approximately 0.55 to approximately 1.85 g (i.e., about 77% of the threshold in normal animals, approximately 2.4 g). Gabapentin did not affect the tactile withdrawal threshold in intact animals. A dose of gabapentin (100 micromol/kg, sc) that had no effect on allodynia was found to significantly reduce the pain behavior during phase 2 of the formalin test. The present study demonstrates that systemic administration of gabapentin suppresses both allodynia induced by an ischemic lesion of the sciatic nerve and pain behavior in the formalin test.
Gustafsson
Henrik
H
In Vivo Pharmacology, Bioscience, AstraZeneca R&D Södertälje, S-141 57, Huddinge, Sweden. henrik.gustafsson@astrazeneca.com
Flood
Karin
K
Berge
Odd Geir
OG
Brodin
Ernst
E
Olgart
Leif
L
Stiller
Carl Olav
CO
D000085:Acetates / Q000097:blood / Q000494:pharmacology*; D000588:Amines; D000700:Analgesics / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003509:Cyclohexanecarboxylic Acids; D004195:Disease Models, Animal; D004923:Erythrosine; D005557:Formaldehyde; D000077206:Gabapentin; D006614:Hindlimb / Q000294:innervation / Q000503:physiopathology; D006930:Hyperalgesia / Q000188:drug therapy* / Q000503:physiopathology; D007834:Lasers; D008027:Light / Q000009:adverse effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D010147:Pain Measurement / Q000187:drug effects*; D010777:Photochemistry; D012584:Sciatic Nerve / Q000187:drug effects / Q000528:radiation effects; D020426:Sciatic Neuropathy / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D005557:Formaldehyde; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D004923:Erythrosine