Microinjection of histamine and its H3 receptor agonist and antagonist into the agranular insular cortex influence sensory and affective components of neuropathic pain in rats

Abstract Many areas of the brain along with neurotransmitters involve in processing of nociceptive, emotional and cognitive dimensions of neuropathic pain. Brian neuronal histamine through H 1 , H 2 , H 3 and H 4 receptors mediates many physiological functions such as cognition, emotion and pain. In the present study we investigated the effects of intra-agranular insular cortex microinjection of histamine and its H 3 receptor agonist and antagonist on sensory and affective aspects of neuropathic pain. Spared nerve injury model of neuropathic pain was used. Two guide cannulas were surgically implanted in the right and left sides of agranular insular cortex. Sensory component (mechanical hyperalgesia) was recorded by application of von Frey filaments onto the plantar surface of the hind paw. Area under curve of mechanical hyperalgesia was calculated. Affective aspect (place escape avoidance paradigm) was recorded using an inverse white/black chamber. Histamine (0.5, 1 and 2 μg/site) and thioperamide (a histamine H 3 receptor antagonist, 4 μg/site) decreased, whereas immepip (a histamine H 3 receptor agonist, 2 μg/site) increased the percentages of paw withdrawal frequency and time spent in white side of white/black box. Prior administration of thioperamide (4 μg/site) increased the suppressive effects induced by histamine and inhibited immepip (2 μg/site)-induced hyperalgesia and aversion. Based on the present results, it is concluded that histamine and its H 3 receptor at the agranular insular cortex level may involve in modulation of sensory and affective components of neuropathic pain.