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.
Kumar
Naresh
N
Department of Anesthesia, McGill University, Montreal, Quebec, Canada H3G 1Y6.
Laferriere
Andre
A
Yu
Jonathan S C
JS
Leavitt
Amelia
A
Coderre
Terence J
TJ
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