Pain
-
The hyperalgesic effects of long-term opioid use in community-dwelling adults with chronic pain have not been widely reported. Therefore, the primary aim of this study was to determine the associations between opioid use and heat pain (HP) perception in a sample of community-dwelling adults with chronic pain. The study cohort involved 187 adults (85 opioid and 102 nonopioid) with chronic pain consecutively admitted to an outpatient interdisciplinary pain treatment program. ⋯ In univariable (P = 0.019) and multiple variable (P = 0.003) linear regression analyses (adjusted for age, sex, body mass index, work status, pain diagnosis, pain severity, depression, and pain catastrophizing), opioid use was associated with lower (more hyperalgesic) nonstandardized values of HP 5-0.5. Similarly, in univariable (P = 0.004) and multiple variable (P = 0.011) linear regression analyses (adjusted for work status, pain diagnosis, pain severity, depression, and pain catastrophizing), opioid use was associated with lower standardized values of HP 5-0.5. In this sample of community-dwelling adults, these observations suggest that long-term opioid use was associated with hyperalgesia independent of other clinical factors known to influence HP perception.
-
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.
-
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.
-
Pain-related functional impairment and behavioral depression are diagnostic indicators of pain and targets for its treatment. Nesting is an innate behavior in mice that may be sensitive to pain manipulations and responsive to analgesics. The goal of this study was to develop and validate a procedure for evaluation of pain-related depression of nesting in mice. ⋯ Neither ketoprofen nor morphine alleviated depression of nesting by U69,593, which suggests that ketoprofen and morphine effects were selective for pain-related depression of nesting. In contrast to ketoprofen and morphine, the kappa opioid receptor antagonist JDTic blocked depression of nesting by U69,593 but not by acid or complete Freund adjuvant. These results support utility of this procedure to assess expression and treatment of pain-related depression in mice.