Spinal somatostatin SSTR2A receptors are preferentially up-regulated and involved in thermonociception but not mechanonociception.

The present study was undertaken to investigate the role of spinal somatostatin SSTR2A receptors in nociceptive processing. SSTR2A receptor-like immunoreactivity was found in a dense network in the spinal cord of normal rats. With Western blot analysis a major band of approximately 80-85 kDa was detected. Both immunohistochemistry and immunoblot analysis indicated a significant increase in SSTR2A receptor content in the spinal cord 6 h after noxious thermal stimulation that lasted for at least 24 h. However, there were no notable changes in SSTR2A receptor content 3, 6, 12, or 24 h after noxious mechanical stimulation. Effects of intrathecally administered polyclonal antiserum to SSTR2A receptor (anti-SSTR2A) on thermal and mechanical pain thresholds were determined with behavioral tests. In normal rats, pretreatment with anti-SSTR2A (1 microl, intrathecal) did not affect paw withdrawal latency or pinch threshold. Hindpaw inflammation induced by complete Freund's adjuvant led to thermal and mechanical hyperalgesia as reflected by a robust decrease in paw withdrawal latency and pinch threshold. Significant attenuation of the thermal hyperalgesia was observed 3, 5, 7, 9, and 24 h after pretreatment with anti-SSTR2A. This effect disappeared in another 24 h. In contrast, pretreatment with anti-SSTR2A failed to exert any notable effect on adjuvant-induced mechanical hyperalgesia. The present findings provide the first evidence that SSTR2A receptors are responsible for thermal, but not mechanical, nociceptive transmission in the spinal cord. The results also suggest that somatostatin has an excitatory role in spinal nociceptive processing and that there are differential receptor responses to different types of noxious stimuli.