Articles: hyperalgesia.
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The present study investigated the role of the amygdala N-methyl-d-aspartate (NMDA) receptors/nitric oxide synthase pathway in morphine-induced anti-allodynia. Concurrently with the bilateral cannulation of the central amygdala, chronic constriction of the sciatic nerve was performed on male Wistar rats. Morphine (3-5 mg/kg) was administered intraperitoneally to induce anti-allodynia. ⋯ PERSPECTIVE: Neuropathic pain is difficult to treat and the exact mechanisms remain unknown. This article suggests the importance of the amygdala glutamatergic and nitric oxide systems in morphine-induced anti-allodynia. These findings might be used in clinical studies to reach a better understanding of neuropathic pain mechanisms and treatment.
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Sphingosine-1-phosphate (S1P) receptor 1 subtype (S1PR1) activation by its ligand S1P in the dorsal horn of the spinal cord causes mechanohypersensitivity. The cellular and molecular pathways remain poorly understood. We report that the activation of S1PR1 with an intrathecal injection of the highly selective S1PR1 agonist SEW2871 led to the development of mechanoallodynia by activating the nod-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome (increased expression of NLRP3, cleaved caspase 1 and mature IL-1β) in the dorsal horn of the spinal cord. ⋯ Our findings provide novel mechanistic insights on how S1PR1 activation in the spinal cord contributes to the development of nociception while identifying the cellular substrate for these activities. PERSPECTIVE: This study is the first to link the activation of NLRP3 and IL-1β signaling in the spinal cord and S1PR1 signaling in astrocytes to the development of S1PR1-evoked mechanoallodynia. These findings provide critical basic science insights to support the development of therapies targeted toward S1PR1.
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Chronic muscle pain is a prominent symptom of the hand-arm vibration syndrome (HAVS), an occupational disease induced by exposure to vibrating power tools, but the underlying mechanism remains unknown. We evaluated the hypothesis that vibration induces an interleukin 6 (IL-6)-mediated downregulation of the potassium voltage-gated channel subfamily A member 4 (KV1.4) in nociceptors leading to muscle pain. Adult male rats were submitted to a protocol of mechanical vibration of the right hind limb. ⋯ Finally, knockdown of the IL-6 receptor signaling subunit glycoprotein 130 (gp130) attenuated both vibration-induced muscle hyperalgesia and downregulation of KV1.4. These results support the hypothesis that IL-6 plays a central role in the induction of muscle pain in HAVS. This likely occurs through intracellular signaling downstream to the IL-6 receptor subunit gp130, which decreases the expression of KV1.4 in nociceptors.
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Animal experiment: a rat model of lumbar disc herniation (LDH) induced painful radiculopathies. ⋯ N/A.
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Neuroscience letters · Jul 2019
ReviewSensitization of nociceptors and dorsal horn neurons contributes to pain in sickle cell disease.
Sickle cell disease (SCD) describes a group of disorders associated with a point mutation in the beta chain of hemoglobin. The mutation leads to the creation of sickle hemoglobin (HbS) and causes distortion of erythrocytes through polymerization under low oxygen, resulting in characteristic sickle red blood cells. Vaso-occlusion episodes caused by accumulation of sRBCs results in ischemia-reperfusion injury, reduced oxygen supply to organs, oxidative stress, organ damage and severe pain that often requires hospitalization and opioid treatment. ⋯ Progress towards the development of novel strategies for both acute and chronic pain in patients with SCD has been impeded by a lack of understanding the mechanisms underlying pain in SCD. The purpose of this review is to highlight evidence for the contribution of peripheral and central sensitization that leads to widespread, chronic pain and hyperalgesia. Targeting the mechanisms that initiate and maintain sensitization in SCD might offer effective approaches to manage the severe and debilitating pain associated with this condition.