Pain
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Activation of histamine H3 receptors (H3Rs) reduces inflammation and nociception, but the existence of H3Rs on peripheral innervation has never been demonstrated. Here we use antibodies to locate H3Rs in whisker pads, hairy and glabrous hind paw skin, dorsal root ganglia (DRGs), and spinal cords of rats, wild type mice, and H3R knockout (H3KO) mice. Although H3Rs have been hypothesized to be on C and sympathetic fibers, H3R-like immunoreactivity (H3R-LI) was only detected on presumptive periarterial A delta fibers and on A beta fibers that terminated in Meissner's corpuscles and as lanceolate endings around hair follicles. ⋯ Low levels of H3R-LI were also present on A beta fibers penetrating superficial and into deeper laminae. The distribution of H3R-LI was similar in rats and wild type mice, but was eliminated or strongly reduced in A delta fibers and A beta fibers, respectively, in H3KO mice. Taken with recently published behavioral results, the present findings suggest that periarterial, peptidergic, H3R-containing A delta fibers may be sources of high threshold mechanical nociception.
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Peripheral nerve injury activates satellite cells to produce interleukin 1beta (IL-1beta) which mediates inflammation and hyperalgesia. This study investigated the hypothesis that activation of satellite glial cells modulates the excitability of trigeminal ganglion (TRG) neurons via IL-1beta following inflammation. Inflammation was induced by injection of complete Freund's adjuvant (CFA) into the whisker pad area. ⋯ The response to IL-1beta was abolished by treatment with the IL-1RI antagonist. These results suggest that activation of satellite glial cells modulates the excitability of small-diameter TRG neurons via IL-1beta following inflammation, and that the upregulation of IL-1RI in the soma may contribute to the mechanism underlying inflammatory hyperalgesia. Therefore IL-1beta blockers are potential therapeutic agents for prevention of trigeminal hyperalgesia.