The value of the International Association for the Study of Pain to career development: perspectives of trainee and early career members.

ABSTRACT: Supporting its young members has been a key priority of the International Association for the Study of Pain (IASP) for the past 5 decades. The IASP, along with its federations, chapters, and special interest groups, has provided benefits to its trainee and early career members for their career development. This article summarizes various key IASP initiatives and benefits offered to IASP members and how these benefits have positively impacted their careers, including examples from the authors of this article. Suggestions are made for future directions that the IASP could implement to enhance the value provided to its trainee and early career members, which will in turn contribute to IASP achieving its mission to stimulate and support the study of pain and to translate that knowledge into improved pain relief worldwide.

Meningeal dendritic cells drive neuropathic pain through elevation of the kynurenine metabolic pathway in mice.

Neuropathic pain is one of the most important clinical consequences of injury to the somatosensory system. Nevertheless, the critical pathophysiological mechanisms involved in neuropathic pain development are poorly understood. In this study, we found that neuropathic pain is abrogated when the kynurenine metabolic pathway (KYNPATH) initiated by the enzyme indoleamine 2,3-dioxygenase 1 (IDO1) is ablated pharmacologically or genetically. Mechanistically, it was found that IDO1-expressing dendritic cells (DCs) accumulated in the dorsal root leptomeninges and led to an increase in kynurenine levels in the spinal cord. In the spinal cord, kynurenine was metabolized by kynurenine-3-monooxygenase-expressing astrocytes into the pronociceptive metabolite 3-hydroxykynurenine. Ultimately, 3-hydroxyanthranilate 3,4-dioxygenase-derived quinolinic acid formed in the final step of the canonical KYNPATH was also involved in neuropathic pain development through the activation of the glutamatergic N-methyl-D-aspartate receptor. In conclusion, these data revealed a role for DCs driving neuropathic pain development through elevation of the KYNPATH. This paradigm offers potential new targets for drug development against this type of chronic pain.

Protective effect of Chresta martii extract on the zymosan-induced temporomandibular joint arthritis in rats.

OBJECTIVE: Chresta martii is broadly used by folk medicine due to its anti-inflammatory effects, but there is a lack of preclinical data on its pharmacological mechanisms. This study investigated the efficacy of Chresta martii ethanolic extract (CEE) in the zymosan-induced temporomandibular joint arthritis (TMJ) and evaluated the possible role of TNF-α, nitric oxide (NO), and heme oxygenase-1 (HO-1). METHODS: Male Wistar rats (160-220 g) were pre-treated with CEE (100, 200 or 400 mg/kg; v.o) 1 h before zymosan injection (2 mg; i.art). Mechanical hypernociception (g) was assessed 4 h later. The trigeminal ganglion was collected for TNF-α quantification (ELISA), total cell count and myeloperoxidase activity (MPO) were assayed in the synovial lavage 6 h after arthritis induction. Additionally, animals were pre-treated with L-NAME (30 mg/kg; i.p.) or ZnPP-IX (3 mg/kg, s.c.) to assess the involvement of NO and HO-1, respectively. RESULTS: CEE 400 mg/kg (v.o) increased (p < 0.05) hypernociception threshold, reduced the cell counts and MPO activity in the synovial lavage, as well as decreased TNF-α levels in the trigeminal ganglion. ZnPP-IX abolished the analgesic effect of CEE, but not L-NAME. CONCLUSION: The anti-inflammatory and antinociceptive effects of CEE depended on the HO-1 pathway integrity and TNF-α suppression.