Effect of spinal PKGIα inhibition on CFA-induced chronic inflammatory pain

Several lines of evidence have demonstrated that a downstream molecule of the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signaling pathway, protein kinase G (PKG), is involved in spinal nociceptive processing^1-3. Our previous studies have shown that PKGIα is abundantly expressed in the superficial laminae at different spinal levels and plays an important role in formalin-induced inflammatory hyperalgesia and N-methyl-D-aspartate- or NO-produced spinal thermal hyperalgesia^4,5. However, it is unclear whether spinal PKGIα is involved in the central mechanisms of chronic pain. In the present study, we investigated the effect of spinal PKGIα inhibition on complete Freund's adjuvant (CFA)-induced chronic inflammatory pain. Rats were given intraplantar injections of saline (100 μl) or CFA (100 μl, 1:1 diluted by saline). We found that CFA injection upregulated the level of PKGIα expression at 24 h and 72 h post-injection, and that intrathecal injection of PKGIα inhibitor Rp-8-CPT-cGMPS (30 μg) significantly inhibited CFA-induced mechanical and thermal hypersensitivity and the PKGIα inhibitor inhibited decreased paw withdrawal threshold and paw withdrawal latency after CFA injection. These results suggest that spinal PKGIα plays an important role in the spinal central sensitization of chronic pain modulation.

References:

1. Schmidtko, Nitric Oxide, 2003

2. Tegeder, Proc. Natl. Acad. Sci. USA, 2004

3. Patil, Inflammopharmacology, 2006

4. Tao, Neuroscience, 2000

5. Tao, Eur. J. Pharmacol., 2000

Acknowledgment of support:

Supported by NIH R01 grants GM049111 and NS44219.