Recent progress in understanding the mechanisms of pain and itch

Ji, Ru-Rong

doi:10.1007/s12264-012-1220-z

Cited by 7 publications

(7 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…18,31 However, the mechanisms by which itch is signaled to the CNS are currently under intense scrutiny and considerable weight has been placed on signaling through specific C-fiber primary afferents. 12,17,25,29,37 Nevertheless, the role of A-fibers in itch signaling is also established, if lacking in molecular detail. 11,34 Thus, our current observations emphasize the role that A-fibers may play in itch signaling and the importance of the mTORC1 pathway in the regulation of some functions of these primary afferents.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of the mammalian target of rapamycin complex 1 signaling pathway reduces itch behaviour in mice

Obara

Medrano

Signoret-Genest

et al. 2015

Pain

View full text Add to dashboard Cite

Activated mammalian target of rapamycin (P-mTOR) has been shown to maintain the sensitivity of subsets of small-diameter primary afferent A-nociceptors. Local or systemic inhibition of the mTOR complex 1 (mTORC1) pathway reduced punctate mechanical and cold sensitivity in neuropathic pain and therefore offered a new approach to chronic pain control. In this study, we have investigated the effects of the rapamycin analog temsirolimus (CCI-779) on itch. Bouts of scratching induced by the histamine-dependent pruritogenic compound 48/80 and histamine-independent pruritogens, chloroquine and SLIGRL-NH2, injected intradermally were significantly reduced by local (intradermal) or systemic (intraperitoneal, i.p.) pretreatment with CCI-779. We also investigated the action of metformin, a drug taken to control type 2 diabetes and recently shown to inhibit mTORC1 in vivo. Although the response to nonhistaminergic stimuli was reduced at all of the time points tested, scratching to compound 48/80 was modified by metformin only when the drug was injected 24 hours before this pruritogen. We also examined the colocalization of P-mTOR with gastrin-releasing peptide, a putative marker for some itch-sensitive primary afferents, and found that P-mTOR was coexpressed in less than 5% of gastrin-releasing peptide-positive fibers in the mouse skin. Taken together, the data highlight the role that P-mTOR-positive A-fibers play in itch signaling and underline the importance of the mTORC1 pathway in the regulation of homeostatic primary afferent functions such as pain and itch. The actions of the antidiabetic drug metformin in ameliorating nonhistamine-mediated itch also suggest a new therapeutic route for the control of this category of pruritus.

show abstract

Section: Discussionmentioning

confidence: 99%

Inhibition of the mammalian target of rapamycin complex 1 signaling pathway reduces itch behaviour in mice

Obara

Medrano

Signoret-Genest

et al. 2015

Pain

View full text Add to dashboard Cite

show abstract

“…It has been demonstrated that histamine injected into the skin elicits itching in a dose-dependent manner, and most experimental itch stimuli act via histamine release from mast cells [24][25][26] . Interestingly, histamine-induced itching shows species-specificity.…”

Section: Discussionmentioning

confidence: 99%

Effects of histamine on spontaneous neuropathic pain induced by peripheral axotomy

Lou

Jia

et al. 2013

Neurosci. Bull.

View full text Add to dashboard Cite

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.

show abstract

“…In 2012, we published the first special issue on mechanisms of pain and itch in Neuroscience Bulletin, which covered the peripheral, central, and glial mechanisms of pain and itch [1][2][3][4][5]. In the last 5 years, the field has seen tremendous progress in the molecular and functional characterization of primary sensory neurons [6,7], neurocircuits of pain and itch [8][9][10], immune and glial modulation of pain and itch [11][12][13][14][15], molecular mechanisms of pain [16,17], and identification of brain signatures of pain [18].…”

mentioning

confidence: 99%