1. A critical time window for the analgesic effect of central histamine in the partial sciatic ligation model of neuropathic pain
- Author
-
Wei Wei Hou, Jiaxing Yue, Ying Ying Tang, Zhong Chen, Jie Yu, Guo Dong Lou, Ting Ting Hu, Li Yun Shi, Shi-Hong Zhang, Hiroshi Ohtsu, and Ran Ran Wang
- Subjects
Central Nervous System ,0301 basic medicine ,Histidine Decarboxylase ,Pharmacology ,Neuropathic pain ,Rats, Sprague-Dawley ,Mice ,chemistry.chemical_compound ,0302 clinical medicine ,Histamine H2 receptor ,Microglial activation ,Mice, Knockout ,Analgesics ,Drug Administration Routes ,General Neuroscience ,Histamine H1 Antagonists ,Histidine decarboxylase ,Histamine H2 Antagonists ,Neurology ,Hyperalgesia ,IL-1β ,Anesthesia ,medicine.symptom ,Cimetidine ,Histamine ,medicine.drug ,Pain Threshold ,Central histamine ,Immunology ,Histamine H1 receptor ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,medicine ,Animals ,Histidine ,Analgesic effect ,Pyrilamine ,business.industry ,Research ,Receptors, Interleukin-1 ,Rats ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,chemistry ,Sciatic Neuropathy ,business ,030217 neurology & neurosurgery - Abstract
Background It is known that histamine participates in pain modulation. However, the effect of central histamine on neuropathic pain is not fully understood. Here, we report a critical time window for the analgesic effect of central histamine in the partial sciatic nerve ligation model of neuropathic pain. Methods Neuropathic pain was induced by partial sciatic nerve ligation (PSL) in rats, wild-type (C57BL/6J) mice and HDC−/− (histidine decarboxylase gene knockout) and IL-1R−/− (interleukin-1 receptor gene knockout) mice. Histidine, a precursor of histamine that can increase the central histamine levels, was administered intraperitoneally (i.p.). Histidine decarboxylase (HDC) enzyme inhibitor α-fluoromethylhistidine was administered intracerebroventricularly (i.c.v.). Histamine H1 receptor antagonist mepyramine and H2 receptor antagonist cimetidine were given intrathecally (i.t.) and intracisternally (i.c.). Withdrawal thresholds to tactile and heat stimuli were measured with a set of von Frey hairs and infrared laser, respectively. Immunohistochemistry and Western blot were carried out to evaluate the morphology of microglia and IL-1β production, respectively. Results Histidine (100 mg/kg, i.p.) administered throughout days 0–3, 0–7, or 0–14 postoperatively (PO) alleviated mechanical allodynia and thermal hyperalgesia in the hindpaw following PSL in rats. Intrathecal histamine reversed PSL-induced thermal hyperalgesia in a dose-dependent manner and intracisternal histamine alleviated both mechanical allodynia and thermal hyperalgesia. Moreover, α-fluoromethylhistidine (i.c.v.) abrogated the analgesic effect of histidine. However, histidine treatment initiated later than the first postoperative day (treatment periods included days 2–3, 4–7, and 8–14 PO) did not show an analgesic effect. In addition, histidine treatment initiated immediately, but not 3 days after PSL, inhibited microglial activation and IL-1β upregulation in the lumbar spinal cord, in parallel with its effects on behavioral hypersensitivity. Moreover, the inhibitory effects on pain hypersensitivity and spinal microglial activation were absent in HDC−/− mice and IL-1R−/− mice. H1 receptor antagonist mepyramine (200 ng/rat i.t. or i.c.), but not H2 receptor antagonist cimetidine (200, 500 ng/rat i.t. or 500 ng/rat i.c.), blocked the effects of histidine on pain behavior and spinal microglia. Conclusions These results demonstrate that central histamine is analgesic within a critical time window in the PSL model of neuropathic pain via histamine H1 receptors. This effect may partly relate to the inhibition of microglial activation and IL-1β production in the spinal cord following nerve injury. Electronic supplementary material The online version of this article (doi:10.1186/s12974-016-0637-0) contains supplementary material, which is available to authorized users.
- Published
- 2016