Articles: hyperalgesia.
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Neuropathic pain takes a heavy toll on individual well-being, while current therapy is far from desirable. Herein, we assessed the analgesic effect of β-elemene, a chief component in the traditional Chinese medicine Curcuma wenyujin, and explored the underlying mechanisms at the level of spinal dorsal horn (SDH) under neuropathic pain. A spared nerve injury (SNI)-induced neuropathic pain model was established in rats. ⋯ SNI significantly increased the expression of p-ERK in spinal astrocytes but not microglia on day 29. β-elemene reversed spinal astrocytic ERK activation and subsequent upregulation of proinflammatory cytokines in SNI rats, with no effect on the expression of p38 and JNK in spinal glia. β-elemene also exerted antioxidative effects by increasing the levels of SOD and GSH-PX and decreasing the level of MDA. Our results suggest that SNI induces robust astrocytic ERK activation within the SDH in the late phase of neuropathic pain. β-elemene exerts remarkable analgesic effects on neuropathic pain, possibly by inhibiting spinal astrocytic ERK activation and subsequent neuroinflammatory processes. Our findings suggest that β-elemene might be a promising analgesic for the treatment of chronic pain.
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DNA hydroxylation catalyzed by Tet dioxygenases occurs abundantly in neurons in mammals. However, effects of ten-eleven translocation methylcytosine dioxygenase 1 (TET1) expression and hydroxymethylation status on neuron injury remain unclear. This study was designed to explore the effects of TET1 and TET2 expression in the inflammatory pain of rats induced by complete Freund's adjuvant (CFA). ⋯ Intrathecal administration of Bobcat339 improved mechanical and thermal pain threshold in CFA rats. Our findings highlight the role of TET1 in chronic inflammatory pain model. The expression of TET1 was increased in CFA rats, and suppression of TET1 will ameliorate inflammatory pain.
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The experimental investigations on the pathogenesis of remifentanil-induced hyperalgesia (RIH) have been primarily conducted, but the effective treatment of RIH remains unclear. Recent reports highlight the necessity of ionotropic glutamate receptors in oxidative damage in spinal nociceptive transduction. Artesunate, the 1st-line anti-malaria drug, has been identified to be valid in removing superoxide in several pathological conditions. ⋯ Moreover, hyperalgesia and peroxiredoxin-3 hyperacetylation were attenuated after the combination of artesunate (1 μg) and MPEP (1 nmol). Additionally, artesunate treatment reversed acute pain and peroxiredoxin-3 hyperacetylation following spinal exposure to DHPG. In conclusion, intrathecal injection of artesunate impairs RIH by down-regulating spinal mGluR5 expression and peroxiredoxin-3 hyperacetylation-mediated oxidative stress in rats.
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► Nausea ►Paresthesia ► Cold allodynia.
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Acute injury-induced pain can transition to chronic nociplastic pain, which predominantly affects women. To facilitate studies on the underlying mechanisms of nociplastic pain, we developed a mouse model in which postinjury thermal stimulation (intermittent 40°C water immersion for 10 minutes at 2 hours postcapsaicin) prolongs capsaicin (ie, experimental injury)-induced transient mechanical hypersensitivity outside of the injury area. Although capsaicin injection alone induced mechanical and thermal hypersensitivity that resolved in ∼7 days (slower recovery in females), the postinjury stimulation prolonged capsaicin-induced mechanical, but not thermal, hypersensitivity up to 3 weeks in both sexes. ⋯ Although morphine and gabapentin effectively alleviated this persistent mechanical hypersensitivity in both sexes, sexually dimorphic mechanisms mediated the hypersensitivity. Specifically, ongoing afferent activity at the previously capsaicin-injected area was critical in females, whereas activated spinal microglia were crucial in males. These results demonstrate that postinjury stimulation of the injured area can trigger the transition from transient pain to nociplastic pain more readily in females, and sex-dependent mechanisms maintain the nociplastic pain state.