Effects of administration of histamine and its H۱, H۲, and H۳ receptor antagonists into the primary somatosensory cortex on inflammatory pain in rats

  Objective(s): The present study investigated the effects of microinjection of histamine and histamine H۱, H۲, and H۳ receptor antagonists, chlorpheniramine, ranitidine and thioperamide, respectively into the primary somatosensory cortex (PSC) on inflammatory pain.   Material and Methods: Two stainless steel guide canulas were bilaterally implanted into the PSC of anaesthetized rats. Inflammatory pain was induced by subcutaneous (SC) injection of formalin (۵۰ μl, ۲.۵%) in the ventral surface of right hind paw. Time durations of licking/biting of the injected paw were recorded as a pain measure. Results: Formalin produced a biphasic pattern of licking/biting of the injected paw. Histamine at doses of ۰.۵, ۱, and ۲ μg decreased the intensity of pain. Chlorpheniramine and ranitidine at the same doses of ۱ and ۴ μg had no effects, whereas thioperamide at a dose of ۴ μg suppressed both phases of formalin-induced pain. Pretreatments with chlorpheniramine and ranitidine at the same dose of ۴ μg prevented histamine (۲ μg)-induced antinociception. Antinociceptive effects were observed when thioperamide at doses of ۱ and ۴ μg was used with ۰.۲۵ and ۱ μg of histamine, respectively. The antinociceptive effects induced by histamine (۲ μg) and thioperamide (۴ μg) were prevented by prior treatment with naloxone (۴ μg). Conclusion: These results indicate that at PSC levels, histamine through post-synaptic H۱, H۲, and pre-synaptic H۳ receptors might be involved in pain modulation. The endogenous opioid system may be involved in histamine- and thioperamide-induced antinociception.

Keywords:

Formalin-induced pain Histamine , Histamine receptor antagonists , Primary somatosensory cortex , Rats