TRPA1 modulation of spontaneous and mechanically evoked firing of spinal neurons in uninjured, osteoarthritic, and inflamed rats.
BACKGROUND
There is growing evidence supporting a role for TRPA1 receptors in the neurotransmission of peripheral mechanical stimulation. In order to enhance understanding of TRPA1 contributions to mechanotransmission, we examined the effects a selective TRPA1 receptor antagonist, A-967079, on spinal neuronal activity following peripheral mechanical stimulation in uninjured, CFA-inflamed, and osteoarthritc (OA) rats.


RESULTS
Systemic injection of A-967079 (30 micromol/kg, i.v.) decreased the responses of wide dynamic range (WDR), and nociceptive specific (NS) neurons following noxious pinch stimulation of the ipsilateral hind paw in uninjured and CFA-inflamed rats. Similarly, A-967079 reduced the responses of WDR neurons to high-intensity mechanical stimulation (300 g von Frey hair) of the knee joint in both OA and OA-sham rats. WDR neuronal responses to low-intensity mechanical stimulation (10 g von Frey hair) were also reduced by A-967079 administration to CFA-inflamed rats, but no effect was observed in uninjured rats. Additionally, the spontaneous activity of WDR neurons was decreased after A-967079 injection in CFA-inflamed rats but was unaltered in uninjured, OA, and OA-sham animals.


CONCLUSIONS
Blockade of TRPA1 receptors disrupts transmission of high-intensity mechanical stimulation to the spinal cord in both uninjured and injured rats indicating that TRPA1 receptors have an important role in noxious mechanosensation in both normal and pathological conditions. TRPA1 receptors also contribute to the transmission of low-intensity mechanical stimulation, and to the modulation of spontaneous WDR firing, but only after an inflammatory injury.
McGaraughty
Steve
S
Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA. Steve.P.McGaraughty@abbott.com
Chu
Katharine L
KL
Perner
Richard J
RJ
Didomenico
Stan
S
Kort
Michael E
ME
Kym
Philip R
PR
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D017487:Ankyrins; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D007249:Inflammation / Q000150:complications / Q000503:physiopathology; D008465:Mechanoreceptors / Q000187:drug effects / Q000502:physiology; D010003:Osteoarthritis / Q000150:complications / Q000503:physiopathology; D010146:Pain / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010812:Physical Stimulation; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels
D017487:Ankyrins; D015220:Calcium Channels; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; C480976:Trpa1 protein, rat