Search

Owing to their functional diversity, the Mas-related G-protein-coupled receptor (Mrgpr) family has a role in both itch and pain modulation. While primarily linked to pruritis, Mrgprs were originally characterized in small-diameter nociceptive neurons of dorsal root ganglia (DRG) and trigeminal ganglia. This review will focus on the role Mrgpr's have in pain physiology, discussing recent discoveries as well as how Mrgpr's may provide a new target for the treatment of pathological pain., (Copyright © 2021 Elsevier B.V. All rights reserved.)

To clarify the involvement of GluR2 and GluR3 subunits of AMPA receptor in orofacial neuropathic pain, we studied changes in nocifensive behavior and extracellular-signal regulated kinase (ERK) phosphorylation followed by infraorbital nerve (ION)-partial transection model applied to GluR2 or GluR3 delta7 knock-in (KI) mice. In these animals, last seven amino acids of GluR2 or GluR3 subunit, the binding sites of interacting protein, are deleted in vivo. Head-withdrawal threshold to mechanical stimulation of the whisker pad skin ipsilateral to ION-partial transection was significantly reduced at 1, 3, 5, 7, 11 and 14 days after transection compared with that before transection in wild-type mice. In the GluR2 and GluR3 delta7 KI mice, the head-withdrawal threshold did not change following ION-partial transection. The number of pERK-LI cells examined in Vc and C1-C2 in wild-type mice after the non-noxious stimulation was larger than that of GluR2 and GluR3 delta7 KI mice. The present findings suggest that GluR2 and GluR3 subunits of AMPA receptor play roles in the trigeminal nerve injury-mediated enhancement of Vc and C1-C2 neuronal excitability, and hyperalgesia., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Painful diabetic neuropathy causes hyperalgesia and does not respond to commonly used analgesics such as non-steroidal anti-inflammatory drugs or opioids at doses below those producing disruptive side effects. In the present study, we examined the effect of P2X receptor antagonists, which are known to modulate the pain pathway, on mechanical hyperalgesia in streptozotocin (STZ)-induced diabetic mice. The paw withdrawal frequency measured by von Frey filaments, began to significantly increase 5 days after STZ injection and was maintained for more than 14 days. Intrathecal administration of P2X receptor antagonists (PPADS and TNP-ATP) inhibited the mechanical allodynia in diabetic mice. The levels of P2X(2) and P2X(3) receptors mRNA were significantly increased in diabetic mice at 14 days after the intravenous injection of STZ. These results suggest that the upregulation of P2X(2), P2X(3) and/or P2X(2/3) receptor in DRG neurons is associated with mechanical allodynia in STZ-induced diabetic mice.

The epidermis is innervated by fine nerve endings that are important in the perception of nociceptive stimuli. However, their role in neuropathic pain is controversial. In this paper, changes in the innervation patterns of epidermal sensory afferent fibres in the rat lower lip have been studied following bilateral chronic constriction injury (CCI) of the mental nerve-a purely sensory branch of the trigeminal nerve. Sections of the lower lip were processed for immunocytochemistry using antibodies against Protein Gene Product (PGP) 9.5 and Calcitonin Gene-Related Peptide (CGRP) to identify the non-peptidergic and the peptidergic populations of nociceptive small diameter primary sensory afferent fibres. Peptidergic fibres co-localised both markers and the non-peptidergic fibres only stained for PGP 9.5 and not for CGRP. We quantified the total fibre length per 6000 microm(2) in the epidermis at several time points following CCI. Our data indicate that both fibre populations were significantly decreased at 2 weeks post-CCI, followed by fibre re-growth at levels above those seen in sham-operated animals at 4 weeks; however, this increase was only statistically significant for the non-peptidergic population. At 8 weeks post-CCI, the fibre lengths of both populations did not differ significantly from shams. This transient hyper-innervation of the epidermis by one subpopulation of nociceptive fibres coincided with the occurrence of spontaneous pain or dysesthetic sensations which we detected in a previous study in the same animal model. Therefore, we speculate that this transient hyper-innervation of the epidermis following injury could play a role in nociception in these animals.

Substance P immunoreactive (SP-IR) nerve fibres were identified using fluorescence immunohistochemistry and the length of the labelled individual nerve fibres was measured using confocal microscopy of whole mounts of the lateral wall of the ankle joint in 2-week-old domestic chicks. In the normal ankle there was an extensive network of SP-IR fibres in the synovial and subsynovial tissue of the joint capsule. Fours hours after injection of sodium urate into the joint space the joint was inflamed and there was a significant reduction in the labelled nerve fibres. These results demonstrate experimentally that painful gouty arthritis produces a neurogenic depletion of substance P from peripheral nerve fibres in the synovial and subsynovial tissue.

Activation of the ventrolateral periaqueductal gray (vlPAG) evokes a reaction of quiescence, immobility, hypotension and bradycardia. Pain of deep somatic or visceral origin also often triggers a reaction of quiescence, immobility, hypotension and bradycardia and further, evokes a selective increase in immediate-early-gene (c-Fos) expression within the vlPAG. Vasodepression evoked from the vlPAG is thought to be mediated by an inhibition of presympathetic neurons within the rostral ventrolateral medulla (RVLM). In this study the prior injection of retrograde tracer into the RVLM was combined with the use of Fos expression as a marker of neuronal activation, to determine if deep (muscle) pain-evoked vasodepression could be mediated by a direct vlPAG-RVLM pathway. It was revealed that intramuscular injection of formalin, in the anaesthetised rat, evoked a significant increase in Fos expression within the caudal vlPAG, and that approximately 25% of the Fos-immunoreactive neurons projected to the RVLM.