Evidence that pregabalin reduces neuropathic pain by inhibiting the spinal release of glutamate.
Pregabalin is an anti-convulsant that successfully treats many neuropathic pain syndromes, although the mechanism of its anti-hyperalgesic action remains elusive. This study aims to help delineate pregabalin's anti-hyperalgesic mechanisms. We assessed the effectiveness of pregabalin at decreasing mechanical and cold hypersensitivity induced in a rat model of neuropathic pain. Thus, we compared the effectiveness of pre- or post-treatment with systemic or intrathecal (i.t.) pregabalin at reducing the development and maintenance of the neuropathic pain symptoms. Pregabalin successfully decreased mechanical and cold hypersensitivity, as a pre-treatment, but was less effective at suppressing cold hypersensitivity when administered as a post-treatment. Furthermore, both i.t. and systemic administration of pregabalin were effective in reducing the behavioral hypersensitivity, with the exception of systemic post-treatment on cold hypersensitivity. We also examined pregabalin's effects at inhibiting hind paw formalin-induced nociception in naïve rats and formalin-induced release of excitatory amino acids in the spinal cord dorsal horn (SCDH) both in naïve rats and in rats with neuropathic pain. Pregabalin dose-dependently reduced nociceptive scores in the formalin test. We also present the first evidence that pregabalin reduces the formalin-induced release of glutamate in SCDH. Furthermore, i.t. pregabalin reduces the enhanced noxious stimulus-induced spinal release of glutamate seen in neuropathic rats. These data suggest that pregabalin reduces neuropathic pain symptoms by inhibiting the release of glutamate in the SCDH.
Department of Anesthesia, McGill University, Montreal, Quebec, Canada H3G 1Y6.
Naresh
N
Kumar
Andre
A
Laferriere
Jonathan S C
JS
Yu
Amelia
A
Leavitt
Terence J
TJ
Coderre
D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004334:Drug Administration Schedule; D004563:Electrochemistry / Q000379:methods; D018698:Glutamic Acid / Q000378:metabolism*; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology; D008297:Male; D017551:Microdialysis / Q000379:methods; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects; D010812:Physical Stimulation / Q000009:adverse effects; D000069583:Pregabalin; D051381:Rats; D020318:Rats, Long-Evans; D012585:Sciatica / Q000188:drug therapy* / Q000473:pathology*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013119:Spinal Cord Injuries / Q000150:complications; D018709:Statistics, Nonparametric; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D000700:Analgesics; D018698:Glutamic Acid; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid