Gabapentin suppresses cutaneous hyperalgesia following heat-capsaicin sensitization.
BACKGROUND
The anticonvulsant gabapentin, proven effective for neuropathic pain in two large, placebo-controlled clinical trials, is widely used for treatment of chronic pain. Preclinical studies have demonstrated analgesic and antiallodynic effects in models involving neuronal sensitization and nerve injury, without affecting acute pain transmission. The aim of the present study was to link data from animal models and clinical trials for chronic pain by investigating the effect of gabapentin on acute nociception and experimentally induced cutaneous hyperalgesia in healthy volunteers.


METHODS
The human experimental hyperalgesia model, the heat-capsaicin sensitization model, was induced in 25 healthy male volunteers. Subjects received oral gabapentin (1,200 mg) or placebo after heat-capsaicin sensitization was established on the forearm. The primary outcome measures were the sizes of the areas of secondary hyperalgesia to von Frey hair and brush stimulation on the forearm. Secondary outcome measures were as follows: (1) size of secondary hyperalgesia area in response to brief thermal sensitization procedure on the thigh; (2) heat pain detection thresholds in normal and sensitized skin; and (3) painfulness of 1 min of 45 degrees C stimulation in normal skin.


RESULTS
Oral gabapentin profoundly suppressed established cutaneous sensitization on the forearm and prevented development of cutaneous sensitization on the thigh. Thermal nociception in normal skin was unchanged. Side effects were modest.


CONCLUSIONS
The results link preclinical findings with results from clinical trials of neuropathic pain. The results further suggest that gabapentin may prove effective in acute pain disorders involving neuronal sensitization, such as postoperative pain and acute herpetic pain, and could prove effective in prevention of chronic pain.
Laboratory of Pain Physiology, Department of Anesthesiology and Intensive Care Medicine, Herlev University Hospital, Herlev, Denmark. jedi@herlevhosp.kbhamt.dk
Jesper
J
Dirks
Karin L
KL
Petersen
Michael C
MC
Rowbotham
Jørgen B
JB
Dahl
D000085:Acetates / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D000328:Adult; D000588:Amines; D000700:Analgesics / Q000627:therapeutic use*; D002211:Capsaicin / Q000494:pharmacology*; D003509:Cyclohexanecarboxylic Acids; D000077206:Gabapentin; D006358:Hot Temperature; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy*; D008297:Male; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D002211:Capsaicin