Mol Pain
-
The quantification of pain intensity in vivo is essential for identifying the mechanisms of various types of pain or for evaluating the effects of different analgesics. A variety of behavioral tests for pain measurement have been devised, but many are limited because animals are physically restricted, which affects pain sensation. In this study, pain assessment was attempted with minimal physical restriction, and voluntary movements of unrestrained animals were used to evaluate the intensities of various types of pain. ⋯ These results suggest that parameters of voluntary movement, such as, number of rearing and total distance moved, are effective indicators of pain intensity for many types of pain and that they can be used to evaluate degree of pain perception.
-
An inositol 1,4,5-trisphosphate binding protein, comprising 2 isoforms termed PRIP-1 and PRIP-2, was identified as a novel modulator for GABAA receptor trafficking. It has been reported that naive PRIP-1 knockout mice have hyperalgesic responses. ⋯ Suppressed expression of PRIPs induces an elevated expression of KCC2 in the spinal cord, resulting in inhibition of nociception and amelioration of neuropathic pain in DKO mice.
-
Noxious stimulation and nerve injury induce an increase in intracellular Ca(2+) concentration ([Ca(2+)]i) via various receptors or ionic channels. While an increase in [Ca(2+)]i excites neurons, [Ca(2+)]i overload elicits cytotoxicity, resulting in cell death. Intracellular Ca(2+) is essential for many signal transduction mechanisms, and its level is precisely regulated by the Ca(2+) extrusion system in the plasma membrane, which includes the Na(+)-Ca(2+) exchanger (NCX). It has been demonstrated that Ca(2+)-ATPase is the primary mechanism for removing [Ca(2+)]i following excitatory activity in trigeminal ganglion (TG) neurons; however, the role of NCXs in this process has yet to be clarified. The goal of this study was to examine the expression/localization of NCXs in TG neurons and to evaluate their functional properties. ⋯ Our results suggest that NCXs in TG neurons play an important role in regulating Ca(2+)-homeostasis and somatosensory information processing by functionally coupling with voltage-dependent Na+ channels.
-
Peripheral nerve injury can have long-term consequences including pain-related manifestations, such as hypersensitivity to cutaneous stimuli, as well as affective and cognitive disturbances, suggesting the involvement of supraspinal mechanisms. Changes in brain structure and cortical function associated with many chronic pain conditions have been reported in the prefrontal cortex (PFC). The PFC is implicated in pain-related co-morbidities such as depression, anxiety and impaired emotional decision-making ability. We recently reported that this region is subject to significant epigenetic reprogramming following peripheral nerve injury, and normalization of pain-related structural, functional and epigenetic abnormalities in the PFC are all associated with effective pain reduction. In this study, we used the Spared Nerve Injury (SNI) model of neuropathic pain to test the hypothesis that peripheral nerve injury triggers persistent long-lasting changes in gene expression in the PFC, which alter functional gene networks, thus providing a possible explanation for chronic pain associated behaviors. ⋯ This study used an unbiased approach to document long-term alterations in gene expression in the brain following peripheral nerve injury. We propose that these changes are maintained as a memory of an insult that is temporally and spatially distant from the initial injury.
-
Pain tolerance is subject to considerable inter-individual variation, which may be influenced by a number of genetic and non-genetic factors. The mu, delta and kappa opioid receptors play a role in pain perception and are thought to mediate different pain modalities. The aim of this study was to explore associations between pain thresholds and gender and genetic variants in the three opioid receptor genes (OPRM, OPRD and OPRK). Experimental multi-modal pain data from previously published studies carried out in healthy Caucasian volunteers were used in order to limit the number of confounders to the study outcome. Data on thermal skin pain (n=36), muscle pressure pain (n=31) and mechanical visceral pain (n=50)) tolerance thresholds were included. ⋯ This is a preliminary and hypothesis generating study due to the relatively small study size. However, significant association between the opioid receptor genes and experimental pain sensitivity supports the influence of genetic variability in pain perception. These findings may be used to generate hypotheses for testing in larger clinical trials of patients with painful conditions.