Pain
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This study investigated the effects of a single administration of 6-(4-methoxyphenyl)-5-methyl-3-pyridinyl-4-isoxazolo[4,5-c]pyridin-4(5H)-one (MMPIP), a negative allosteric modulator (NAM) of metabotropic glutamate receptor 7 (mGluR7), on pain and on affective and cognitive behavior in neuropathic mice. The activity of pyramidal neurons in the prelimbic cortex (PLC), which respond to stimulation of the basolateral amygdala (BLA) with either excitation or inhibition, was also investigated. The spared nerve injury (SNI) of the sciatic nerve induced, 14 days after surgery, thermal hyperalgesia and mechanical allodynia, reduced open-arm choice in the elevated plus-maze, increased time of immobility in the tail suspension, and increased digging and burying in the marble burying test. ⋯ It reduced the immobility in the tail suspension test and the number of marbles buried and of digging events in the marble burying test. MMPIP also improved cognitive performance and restored the balance between excitatory and inhibitory responses of PLC neurons in SNI mice. 7-hydroxy-3-(4-iodophenoxy)-4H-chromen-4-one, XAP044, another selective mGluR7 NAM, reproduced the effects of MMPIP on thermal hyperalgesia, mechanical allodynia, tail suspension, and marble burying test. Altogether, these findings show that mGluR7 NAMs reduce pain responses and affective/cognitive impairments in neuropathic pain conditions.
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Randomized Controlled Trial
Self-reports of medication side effects and pain-related activity interference in patients with chronic pain: A longitudinal cohort study.
The primary purpose of this study was to examine the association between self-reports of medication side effects and pain-related activity interference in patients with chronic pain. The potential moderators of the association between reports of side effects and pain-related activity interference were also examined. A total of 111 patients with chronic musculoskeletal pain were asked to provide, once a month for a period of 6 months, self-reports of medication use and the presence of any perceived side effects (eg, nausea, dizziness, headaches) associated with their medications. ⋯ Importantly, multilevel models revealed that perceived medication side effects were associated with heightened pain-related activity interference even after controlling for the influence of patient demographics, pain intensity, and negative affect. This study provides preliminary evidence that reports of medication side effects are associated with heightened pain-related activity interference in patients with chronic pain beyond the influence of other pain-relevant variables. The implications of our findings for clinical practice and the management of patients with chronic pain conditions are discussed.
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Decreased spinal cord GABAergic inhibition is a major contributor to the persistent neuropathic pain that can follow peripheral nerve injury. Recently, we reported that restoring spinal cord GABAergic signaling by intraspinal transplantation of cortical precursors of GABAergic interneurons from the embryonic medial ganglionic eminence (MGE) can reverse the mechanical hypersensitivity (allodynia) that characterizes a neuropathic pain model in the mouse. ⋯ Transplants from these mice, in which GABA is synthesized but cannot be stored or released, had no effect on mechanical hypersensitivity or heat hyperalgesia in the paclitaxel model. Taken together, these results demonstrate the therapeutic potential of GABAergic precursor cell transplantation in diverse neuropathic pain models and support our contention that restoration of inhibitory controls through release of GABA from the transplants is their mode of action.