Effects of histamine on spontaneous neuropathic pain induced by peripheral axotomy

Abstract

The present study was designed to investigate the effects of histamine on spontaneous neuropathic pain (NP) induced by peripheral axotomy. Rats and mice were subjected to complete transection of the left sciatic and saphenous nerves to induce spontaneous NP (the neuroma model). Rats were then treated with drugs once daily for 30 days (histidine and loratadine, i.p.) or 21 days (histamine, i.c.v.). Autotomy behavior was scored daily until day 50 post-operation (PO). On days 14 to 21 PO, some rats in the control group were subjected to single-fiber recording. Autotomy behavior was also monitored daily in histidine decarboxylase (the key enzyme for histamine synthesis) knockout (HDC -/-) and wild-type mice for 42 days.We found that both histidine (500 mg/kg) (a precursor of histamine that increases histamine levels in the tissues) and histamine (50 µg/5 µL) significantly suppressed autotomy behavior in rats. HDC -/-mice lacking endogenous histamine showed higher levels of autotomy than the wild-type. In addition, the analgesic effect of histidine was not antagonized by loratadine (a peripherally-acting H 1 receptor antagonist), while loratadine alone significantly suppressed autotomy. Electrophysiological recording showed that ectopic spontaneous discharges from the neuroma were blocked by systemic diphenhydramine (an H 1 receptor antagonist). Our results suggest that histamine plays an important role in spontaneous NP. It is likely that histamine in the central nervous system is analgesic, while in the periphery, via H 1 receptors, it is algesic. This study justifies the avoidance of a histamine-rich diet and the use of peripherally-acting H 1 receptor antagonists as well as agents that improve histamine action in the central nervous system in patients with spontaneous NP.

Toll-like receptor 4 contributes to chronic itch, alloknesis, and spinal astrocyte activation in male mice

“…Itch and pain are two distinct somatic sensations, but they also share many similarities [4;18;29;34;36;47;68;69]. Itch evokes scratching response, while pain elicits withdrawal reflex [22].…”

Dynamics of Pain Tolerance Thresholds and Humoral Immunity Factors at Dorsalgy

“…Кро-ме того, оказалось, что женщины хуже переносят боль, чем мужчины. Такие гендерные тенденции согласуются с литературными данными о восприятии боли [20][21][22]. Это связывают с низкой активностью антиноцицептив-ных механизмов у женщин.…”

Histamine Upregulates Nav1.8 Expression in Primary Afferent Neurons via H2 Receptors: Involvement in Neuropathic Pain

“…or vehicle when the autotomy score reached 3 or 4 points. The effect of H 1 receptor antagonist loratadine on autotomy had been reported by us elsewhere and was not included in the present study.…”