Abstract
Orexins are synthesized specifically by neurons in the hypothalamus and contribute to multiple physiological functions. Orexin fibers innervate many regions of the CNS, which include the spinal dorsal horn and areas involved in descending control of pain. We examined the possible role that orexin may play in endogenous modulation of pain transmission using orexin knockout mice. We utilized two conditions that are known to activate endogenous pain modulation systems, i.e. persistent pain and stress, and compared the changes in pain thresholds induced by these conditions in knockout and wild type mice. Inflammation was induced by carrageenan injection to produce persistent pain and electric foot shocks were used to apply stress. Pain thresholds were determined by the paw withdrawal or tail flick test. Baseline pain thresholds of knockout mice were not different from wild type mice. Knockout mice presented greater degree of hyperalgesia induced by peripheral inflammation and less stress-induced analgesia than wild type mice. Furthermore, in an immunohistochemistry study, we examined whether these two conditions were able to induce activation of orexin neurons. Double-staining of orexin and c-Fos in the hypothalamus of wild type mice revealed that orexin neurons were activated under the two conditions. The results suggest that both persistent pain and stress activate orexin pathways which act to inhibit pain transmission. [Jpn J Physiol 55 Suppl:S156 (2005)]
