Differential effects of neuropathic analgesics on wind-up-like pain and somatosensory function in healthy volunteers.
OBJECTIVE
To investigate the effects of gabapentin, carbamazepine, and amitriptyline on temporal summation, simple nociceptive pain, and innocuous touch sensation in healthy volunteers.


METHODS
A placebo controlled four-way crossover double-blind randomized protocol was followed. Seventeen healthy subjects, male and female, aged 18 to 24, took part. Punctate pain, temporal summation pain to repeat punctate stimulation, and vibration detection threshold were assessed in triplicate. Study drugs were given as bedtime and early morning doses with assessments carried out midmorning.


RESULTS
Gabapentin and carbamazepine significantly reduced the intensity of temporal summation pain (P < 0.001 and P < 0.01 respectively), whereas amitriptyline significantly increased temporal summation pain (P < 0.001). None of the drugs affected pain produced by a single punctate stimulus (P > 0.05). Carbamazepine increased vibration detection thresholds (P < 0.05), but neither gabapentin nor amitriptyline had any detectable effect on vibration.


CONCLUSIONS
We have shown that gabapentin, carbamazepine, and amitriptyline, three pharmacologically different drugs, have distinct and quantifiable effects on somatosensory pathways in healthy volunteers. These findings provide a link between pharmacology of the study drugs and clinical effectiveness. The effects of gabapentin and carbamazepine on temporal summation pain show that these drugs can block centrally amplified wind-up pain in the absence of a neuropathic disorder.
Harding
Louise M
LM
The Pain Management Centre, University College London Hospitals NHS Trust, The National Hospital for Neurology and Neurosurgery, Queen Square, London, United Kingdom. louise.harding@uclh.org
Kristensen
Jens D
JD
Baranowski
Andrew P
AP
D000293:Adolescent; D000328:Adult; D000588:Amines / Q000008:administration & dosage*; D000639:Amitriptyline / Q000008:administration & dosage*; D000700:Analgesics / Q000008:administration & dosage; D002220:Carbamazepine / Q000008:administration & dosage*; D018592:Cross-Over Studies; D003509:Cyclohexanecarboxylic Acids / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D000077206:Gabapentin; D006801:Humans; D008297:Male; D009437:Neuralgia / Q000175:diagnosis* / Q000503:physiopathology / Q000517:prevention & control*; D017288:Pain Threshold / Q000187:drug effects; D015990:Placebo Effect; D014110:Touch / Q000187:drug effects*; D016896:Treatment Outcome; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage*
D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D000639:Amitriptyline; D002220:Carbamazepine; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin