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The most frequently used local anesthetics (LA) by the infiltrative route have an ionizable amine in the range of pH 7.6-8.9. Effective anesthesia of inflamed tissues is a great challenge,...

Several recent studies have established the efficacy of photobiomodulation therapy (PBMT) in painful clinical conditions. Diabetic neuropathy (DN) can be related to activating mitogen-activated protein kinases (MAPK), such as p38, in the peripheral nerve. MAPK pathway is activated in response to extracellular stimuli, including interleukins TNF-α and IL-1β. We verified the pain relief potential of PBMT in streptozotocin (STZ)-induced diabetic neuropathic rats and its influence on the MAPK pathway regulation and calcium (Ca2+) dynamics. We then observed that PBMT applied to the L4-L5 dorsal root ganglion (DRG) region reduced the intensity of hyperalgesia, decreased TNF-α and IL-1β levels, and p38-MAPK mRNA expression in DRG of diabetic neuropathic rats. DN induced the activation of phosphorylated p38 (p-38) MAPK co-localized with TRPV1+ neurons; PBMT partially prevented p-38 activation. DN was related to an increase of p38-MAPK expression due to proinflammatory interleukins, and the PBMT (904 nm) treatment counteracted this condition. Also, the sensitization of DRG neurons by the hyperglycemic condition demonstrated during the Ca2+ dynamics was reduced by PBMT, contributing to its anti-hyperalgesic effects.

Millions of people suffer from arthritis worldwide, consistently struggling with daily activities due to debilitating pain evoked by this disease. Perhaps the most intensively investigated type of inflammatory arthritis is rheumatoid arthritis (RA), where, despite considerable advances in research and clinical management, gaps regarding the neuroimmune interactions that guide inflammation and chronic pain in this disease remain to be clarified. The pain and inflammation associated with arthritis are not isolated to the joints, and inflammatory mechanisms induced by different immune and glial cells in other tissues may affect the development of chronic pain that results from the disease. This review aims to provide an overview of the state-of-the-art research on the roles that innate immune, and glial cells play in the onset and maintenance of arthritis-associated pain, reviewing nociceptive pathways from the joint through the dorsal root ganglion, spinal circuits, and different structures in the brain. We will focus on the cellular mechanisms related to neuroinflammation and pain, and treatments targeting these mechanisms from the periphery and the CNS. A comprehensive understanding of the role these cells play in peripheral inflammation and initiation of pain and the central pathways in the spinal cord and brain will facilitate identifying new targets and pathways to aide in developing therapeutic strategies to treat joint pain associated with RA.

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In ammation is a vital process for the injured tissue restoration and one of its hallmarks is in ammatory hyperalgesia. The cyclooxygenase (COX) pathway is strongly related to the in ammatory and painful process. Usually, the COX-1 isoform is described as homeostatic, while COX-2 is characterized as inducible in in ammatory conditions. Although it is well known that neutrophil cells are the rst to arrive at the in amed site and the major source of COX-2 is still unknown the speci c role of neutrophil-derived Cox-2 in the pain process is. Thus, in the present study, we demonstrate for the rst time that neutrophilderived COX-2 plays a key role in peripheral in ammatory hyperalgesia. Conditional knockout mice for Cox-2 in neutrophils (Cox-2 / : Mrp8cre+/− ) exhibited higher pain sensitivity after carrageenan (CG) injection and long-lasting IL-1β-induced hyperalgesia compared with the control group (COX-2 / ). Also, CGinduced in ammation in Cox-2 / : Mrp8cre+/− mice showed Cox-1 overexpression, and increased neutrophil migration and pro-in ammatory cytokines (e.g., IL-1β and CXCL1). These ndings revealed that neutrophil Cox-2 has an important role in the regulation of in ammatory hyperalgesia.

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