Mol Pain
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Matrix metalloproteinases (MMPs) have been suggested to contribute to long-term potentiation, behavioral learning, and memory. In the dorsal horn of spinal cord, MMPs were reported to contribute to injury-related changes, and inhibitors of MMPs have been proposed as potential analgesics. However, it is unclear whether MMP inhibitors produce these effects by inhibiting the function of N-methyl-D-aspartate receptor (NMDAR), a key receptor for the induction of long-term potentiation. ⋯ However, MMP-3 and broad-spectrum MMP inhibitors reduced the NMDAR-mediated excitatory postsynaptic currents. Consistently, MMP-9 and MMP-2/9 inhibitors had no effect on NMDAR-dependent long-term potentiation, but MMP-3 and broad-spectrum MMP inhibitors inhibited the induction of long-term potentiation. Our results suggest that MMP inhibitors may produce their effects by inhibiting NMDAR functions in central synapses.
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Effective pharmacological treatment options for chronic pain remain very limited, and continued reliance on opioid analgesics has contributed to an epidemic in the United States. On the other hand, nonpharmacologic neuromodulatory interventions provide a promising avenue for relief of chronic pain without the complications of dependence and addiction. An especially attractive neuromodulation strategy is to optimize endogenous pain regulatory circuits. ⋯ We showed that low-frequency electrical stimulation of the prelimbic region of the prefrontal cortex relieved both sensory and affective responses to acute pain in naive rats. Furthermore, we found that low-frequency electrical stimulation of the prefrontal cortex also attenuated mechanical allodynia in a rat model of chronic pain. Together, our findings demonstrated that low-frequency electrical stimulation of the prefrontal cortex represents a promising new method of neuromodulation to inhibit pain.
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Neuroimaging studies have demonstrated that reward system is associated with chronic pain diseases. In addition, previous studies have also demonstrated abnormal functional and structural brain regions in primary dysmenorrhea. However, the relation of reward system and primary dysmenorrhea is still unknown. ⋯ Compared to healthy controls, primary dysmenorrhea patients showed decreased connectivity of left nucleus accumbens with the bilateral anterior insula and the left amygdala and decreased connectivity of right nucleus accumbens with ventral tegmental area, the left hippocampus, the right orbital frontal cortex, and the right anterior insula. In addition, the decreased functional connectivity between the right nucleus accumbens-ventral tegmental area negatively correlated with the level of prostaglandin F2 alpha. Our findings provide neuroimaging evidence in support of the abnormal reward system connectivity in primary dysmenorrhea patients, which might contribute to a better understanding of the cerebral pathophysiology of primary dysmenorrhea.
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A well-recognized relationship exists between aging and increased susceptibility to chronic pain conditions, underpinning the view that pain signaling pathways differ in aged individuals. Yet despite the higher prevalence of altered pain states among the elderly, the majority of preclinical work studying mechanisms of aberrant sensory processing are conducted in juvenile or young adult animals. This mismatch is especially true for electrophysiological studies where patch clamp recordings from aged tissue are generally viewed as particularly challenging. ⋯ Specifically, aged dorsal horn neurons more readily exhibit repetitive action potential discharge, indicative of a more excitable phenotype. This observation was accompanied by a decrease in the amplitude and charge of spontaneous excitatory synaptic input to dorsal horn neurons and an increase in the contribution of GABAergic signaling to spontaneous inhibitory synaptic input in aged recordings. While the functional significance of these altered circuit properties remains to be determined, future work should seek to assess whether such features may render the aged dorsal horn more susceptible to aberrant injury or disease-induced signaling and contribute to increased pain in the elderly.
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Morphine is the most commonly used drug for treating physical and psychological suffering caused by advanced cancer. Although morphine is known to elicit multiple supraspinal analgesic effects, its behavioral correlates with respect to the whole-brain metabolic activity during cancer-induced bone pain have not been elucidated. We injected 4T1 mouse breast cancer cells into the left femur bone marrow cavity of BALB/c mice. ⋯ Furthermore, morphine activated the amygdala and rostral ventromedial medulla and suppressed the activity of anterior cingulate cortex. Our findings of hypothalamic and insular cortical activation support the hypothesis that cancer-induced bone pain has strong inflammatory and affective components in freely moving animals. Morphine may provide descending inhibitory and facilitatory actions in the treatment of cancer-induced bone pain in a clinical setting.