Gabapentin and pregabalin suppress tactile allodynia and potentiate spinal cord stimulation in a model of neuropathy.
Spinal cord stimulation (SCS) is an effective tool in alleviating neuropathic pain. However, a number of well-selected patients fail to obtain satisfactory pain relief. Previous studies have demonstrated that i.t. baclofen and/or adenosine can enhance the SCS effect, but this combined therapy has been shown to be useful in less than half of the cases and more effective substances are therefore needed. The aim of this experimental study in rats was to examine whether gabapentin or pregabalin attenuates tactile allodynia following partial sciatic nerve injury and whether subeffective doses of these drugs can potentiate the effects of SCS in rats which do not respond to SCS. Mononeuropathy was produced by a photochemically induced ischaemic lesion of the sciatic nerve. Tactile withdrawal thresholds were assessed with von Frey filaments. Effects of increasing doses of gabapentin and pregabalin (i.t. and i.v.) on the withdrawal thresholds were analysed. These drugs were found to reduce tactile allodynia in a dose-dependent manner. In SCS non-responding rats, i.e. where stimulation per se failed to suppress allodynia, a combination of SCS and subeffective doses of the drugs markedly attenuated allodynia. In subsequent acute experiments, extracellular recordings from wide dynamic range neurones in the dorsal horn showed prominent hyperexcitability. The combination of SCS and gabapentin, at the same subeffective dose, clearly enhanced suppression of this hyperexcitability. In conclusion, electrical therapy and pharmacological therapy in neuropathic pain can, when they are inefficient individually, become effective when combined.
Wallin
Johan
J
Department of Clinical Neuroscience, Section of Neurosurgery, Karolinska Institutet, S-171 76 Stockholm, Sweden.
Cui
Jian-Guo
JG
Yakhnitsa
Vadim
V
Schechtmann
Gastón
G
Meyerson
Björn A
BA
Linderoth
Bengt
B
D000085:Acetates / Q000494:pharmacology*; D000588:Amines; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003509:Cyclohexanecarboxylic Acids; D004359:Drug Therapy, Combination; D004558:Electric Stimulation; D004594:Electrophysiology; D000077206:Gabapentin; D007267:Injections; D007511:Ischemia; D008297:Male; D020422:Mononeuropathies / Q000188:drug therapy* / Q000628:therapy; D010146:Pain / Q000188:drug therapy*; D059408:Pain Management; D020671:Posterior Horn Cells / Q000187:drug effects; D000069583:Pregabalin; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000293:injuries*; D013116:Spinal Cord / Q000187:drug effects*; D014110:Touch; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000085:Acetates; D000588:Amines; D000700:Analgesics; D000927:Anticonvulsants; D002121:Calcium Channel Blockers; D003509:Cyclohexanecarboxylic Acids; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin