Mol Pain
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Beta 2 adrenergic receptor (β2 AR) activation in the central and peripheral nervous system has been implicated in nociceptive processing in acute and chronic pain settings with anti-inflammatory and anti-allodynic effects of β2-AR mimetics reported in several pain states. In the current study, we examined the therapeutic efficacy of the β2-AR agonist clenbuterol in a rat model of persistent postsurgical hypersensitivity induced by disruption of descending noradrenergic signaling in rats with plantar incision. We used growth curve modeling of ipsilateral mechanical paw withdrawal thresholds following incision to examine effects of treatment on postoperative trajectories. ⋯ Direct spinal infusion of clenbuterol failed to reduce mechanical hypersensitivity in depleted rats with incision suggesting that beneficial effects of β2-AR stimulation in this model are largely peripherally mediated. Lastly, we examined β2-AR distribution in the spinal cord and skin using in-situ hybridization and IHC. These data add to our understanding of the role of β2-ARs in the nervous system on hypersensitivity after surgical incision and extend previously observed anti-inflammatory actions of β2-AR agonists to models of surgical injury.
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Rotator cuff tears (RCTs) are often associated with severe shoulder pain. Non-steroidal anti-inflammatory drugs, not recommended for long-term use, do not effectively manage RCT-induced pain, resulting in reduced quality of life. To improve management, a better understanding of the fundamental properties of RCT pain is needed. Here, we aimed to compare the expression levels of nerve growth factor (NGF) and cyclooxygenase-2 (COX-2) mRNA in the synovial tissues of patients with RCT-induced pain and patients with non-painful recurrent shoulder dislocation (RSD). ⋯ NGF mRNA and protein levels were elevated in patients with painful RCT compared with those in patients with non-painful RSD, whereas COX-2 levels were comparable in the two patient groups. These findings provide insights into novel potential strategies for clinical management of RCT.
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Complex regional pain syndrome (CRPS) is a progressive and painful disease of the extremities that is characterized by continuous pain inconsistent with the initial trauma. CRPS is caused by a multi-mechanism process that involves both the peripheral and central nervous system, with a prominent role of inflammation in CRPS pathophysiology. This review examines what is currently known about the CRPS inflammatory and pain mechanisms, as well as the possible impact of neurostimulation therapies on the neuroimmune axis of CRPS. ⋯ Increasing evidence supports a role for inflammation and neuroinflammation in CRPS pathophysiology. Preliminary neurostimulation findings, together with the role of (neuro)inflammation in CRPS, seems to provide a compelling rationale for its use in CRPS pain treatment. The possible immunomodulatory effects of neurostimulation opens new therapeutic possibilities, however further research is needed to gain a better understanding of the working mechanisms.
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Migraine is the second most prevalent disorder in the world; yet, its underlying mechanisms are still poorly understood. Cumulative studies have revealed pivotal roles of cerebral cortex in the initiation, propagation, and termination of migraine attacks as well as the interictal phase. ⋯ We aim to summarize the current research literatures and give a brief overview of the cortex and its role in migraine, including the basic structure and function; structural, functional, and biochemical neuroimaging; migraine-related genes; and theories related to cortex in migraine pathophysiology. We propose that long-term plasticity of synaptic transmission in the cortex encodes migraine.
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Although microglia activation plays an important role in the development of nerve injury-induced neuropathic pain, the molecular mechanisms of spinal cord microglia activation in nerve injury are not completely understood. Recently, two injured sensory neuron-derived molecules, colony stimulating factor-1 (CSF-1) and GT1b, were proposed to trigger spinal cord microglia activation, yet their relationship and relative contribution to microglia activation have not been addressed. In the present study, the role of GT1b and CSF-1 in microglia activation and proliferation was characterized. ⋯ Conversely, CSF-1 stimulation induced microglia proliferation with minimal proinflammatory gene induction. Notably, neither GT1b nor CSF-1 induced mechanical hypersensitivity in female mice; however, they induced similar microglial proliferation in both male and female mice. Taken together, our data indicate that injured sensory neuron-derived GT1b and CSF-1 activate spinal cord microglia in concert through distinct activation pathways.