Effects of histamine receptor antagonists injected intrathecally on antinociception induced by opioids administered intracerebroventricularly in the mouse

The present study was designed to investigate the modulatory effects of blo ckade of spinal histamine receptors on antinociception induced by supraspin ally administered mu-, epsilon-, delta-, and kappa-opioid receptor agonists . The effects of intrathecal (i.t.) injections with cyproheptadine [a hista mine-1 (H1) receptor antagonist], ranitidine (a H2 receptor antagonist), or thioperamide (a H3 receptor antagonist) injected i.t., on the antinocicept ion induced by morphine (a mu-receptor antagonist), beta-endorphin (an epsi lon-receptor agonist), D-Pen(2,5)-enkephalin (DPDPE, a delta-receptor agoni st) or trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl) cyclohxyl] benzeoc etamide (U50,488H, a Ir-receptor agonist) injected intracerebroventricularl y (i.c.v.) were studied. The antinociception was assayed using the tail-fli ck test. The i.t. injection of cyproheptadine (from 0.31 to 62 nmole), rani tidine (from 0.28 to 56 nmole), or thioperamide (from 0.24 to 48 nmole) alo ne did not show any antinociceptive effect. The i.t. pretreatment with cypr oheptadine or thioperamide dose-dependently attenuated the inhibition of th e tail-flick response induced by i.c.v. administered morphine (0.6 nmole), b-endorphin (0.03 nmole), DPDPE (1.5 nmole), and U50,488H (130 nmole). In a ddition, the i.t. pretreatment with ranitidine dose-dependently attenuated the inhibition of the tail-flick response induced by morphine, b-endorphin and U50,488H without affecting DPDPE-induced response. Our results suggest that spinal histamine Hi and H3 receptors may involved in the production of antinociception induced by supraspinally applied morphine, b-endorphin, DP DPE and U50,488H. Spinal H2 receptors appear to be involved in supraspinall y administered morphine, b-endorphin- and U50,488H-induced antinociception but not DPDPE-induced antinociception.