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To investigate the specific effect of insomnia on neuropsychological functioning in patients with very complex chronic pain.
Learn More >Transient receptor potential (TRP) channels are a family of functionally diverse and widely expressed cation channels involved in a variety of cell signaling and sensory pathways. Research in the last two decades has not only shed light on the physiological roles of the 28 mammalian TRP channels, but also revealed the involvement of specific TRP channels in a plethora of inherited and acquired human diseases. Considering the historical successes of other types of ion channels as therapeutic drug targets, small molecules that target specific TRP channels hold promise as treatments for a variety of human conditions. In recent research, important new findings have highlighted the central role of TRP channels in chronic pain, lower urinary tract disorders, and type 2 diabetes, conditions with an unmet medical need. Here, we discuss how these advances support the development of TRP-channel-based pharmacotherapies as valuable alternatives to the current mainstays of treatment.
Learn More >The mechanisms underlying chronic and neuropathic pain pathology involve peripheral and central sensitisation. The medial prefrontal cortex (mPFC) seems to participate in pain chronification, and glutamatergic neurotransmission may be involved in this process. Thus, the aim of the present work was to investigate the participation of the prelimbic (PrL) area of the mPFC in neuropathic pain as well as the role of N-methyl D-aspartate (NMDA) glutamate receptors in neuropathic pain induced by a modified sciatic nerve chronic constriction injury (CCI) protocol in Wistar rats. Neural inputs to the PrL cortex were inactivated by intracortical treatment with the synapse blocker cobalt chloride (CoCl, 1.0 mM/200 nL) 7, 14, 21, or 28 days after the CCI or sham procedure. The glutamatergic agonist NMDA (0.25, 1 or 4 nmol) or the selective NMDA receptor antagonist LY235959 (2, 4 or 8 nmol) was microinjected into the PrL cortex 21 days after surgery. CoCl administration in the PrL cortex decreased allodynia 21 and 28 days after CCI. NMDA at 1 and 4 nmol increased allodynia, whereas LY235959 decreased mechanical allodynia at the highest dose (8 nmol) microinjected into the PrL cortex. These findings suggest that NMDA receptors in the PrL cortex participate in enhancing the late phase of mechanical allodynia after NMDA-induced increases and LY235959-induced decreases in allodynia 21 days after CCI. The glutamatergic system potentiates chronic neuropathic pain by NMDA receptor activation in the PrL cortex. Mechanism of neuropathic pain. The infusion of CoCl, a synapse activity blocker, into the prelimbic (PrL) division of the medial prefrontal cortex (mPFC) decreased the severity of mechanical allodynia, showing the late participation of the limbic cortex. The glutamatergic system potentiates chronic neuropathic pain via NMDA receptor activation in the PrL cortex.
Learn More >Tolerance to the antinociceptive effect of mu-opioid receptor (MOPr) agonists, such as morphine and fentanyl, greatly limits their effectiveness for long-term use to treat pain. Clinical studies have shown that combination therapy and opioid rotation can be used to enhance opioid-induced antinociception once tolerance has developed. The mechanism and brain regions involved in these processes are unknown. The purpose of this study was to evaluate the contribution of the ventrolateral periaqueductal gray (vlPAG) to antinociceptive tolerance and cross-tolerance between administration and co-administration of morphine and fentanyl. Tolerance was induced by pretreating rats with morphine or fentanyl or low-dose combination of morphine and fentanyl into the vlPAG followed by assessment of cross-tolerance to the other opioid. In addition, tolerance to the combined treatment was assessed. Cross-tolerance did not develop between repeated vlPAG microinjections of morphine and fentanyl. Likewise, there was no evidence of cross-tolerance from morphine or fentanyl to co-administration of morphine and fentanyl. Co-administration did not cause cross-tolerance to fentanyl. Cross-tolerance was only evident to morphine or morphine and fentanyl combined in rats pretreated with co-administration of low-doses of morphine and fentanyl. In conclusion, cross-tolerance does not develop between morphine and fentanyl within the vlPAG. This finding is consistent with the functionally selective signaling that has been reported for antinociception and tolerance following morphine and fentanyl binding to the MOPr. This research supports the notion that combination therapy and opioid rotation may be useful clinical practices to reduce opioid tolerance and other side effects. Perspective: This preclinical study shows that there is a reduction in cross tolerance between morphine and fentanyl within the periaqueductal gray which is key brain region in opioid antinociception and tolerance.
Learn More >Much of the opioid epidemic arose from abuse of prescription opioid drugs. This study sought to determine if the combination of a cannabinoid with an opioid could produce additive or synergistic effects on pain, allowing reduction in the opioid dose needed for maximal analgesia.
Learn More >In this issue you will find a paper by Vibe Fersum et al., entitled "Cognitive Functional Therapy in Patients with Non Specific Chronic Low Back Pain: A Randomized Controlled Trial 3-year Follow Up" (Vibe Fersum 2019). This article is protected by copyright. All rights reserved.
Learn More >Musculoskeletal pain is associated with altered motor control that despite short-term benefit, is hypothesised to have long-term consequences, contributing to the development of chronic pain. However, data on how motor control is altered when pain is sustained beyond a transient event are scarce. Here, we investigated motor adaptation, and its relationship to corticomotor excitability, in the transition to sustained muscle pain. Twenty-eight healthy individuals were injected with nerve growth factor (NGF) into the right extensor carpi radialis brevis (ECRB) muscle on Days 0 and 2. Motor adaptation and corticomotor excitability were assessed on Day -2, prior to injection on Days 0 and 2, and again on Days 4 and 14. Motor adaptation was quantified during a radial-ulnar movement as kinematic variability of wrist flexion-extension and pronation-supination, and as electromyographic (EMG) variability of ECRB activity. Pain, muscle soreness, and functional limitation were assessed from Days 0-14. Pain, muscle soreness and functional limitation were evident at Days 2 and 4 (p<0.001). EMG variability reduced at Days 4 and 14 (p<0.04), with no change in kinematic variability (p=0.9). However, data revealed variation in EMG and kinematic variability between individuals: some displayed increased motor variability while others a decrease. Individuals who displayed an increase in EMG variability following four days of pain also displayed an increase in corticomotor excitability (r=0.43, p=0.034). These findings suggest individual adaptation of the motor system in the transition to sustained pain that could have implications for clinical musculoskeletal pain disorders.
Learn More >To identify migraineurs and headache-free individuals with an online questionnaire and automated analysis algorithm.
Learn More >Chronic widespread pain (CWP) is common and associated with loss of functioning and health. Subjects with chronic non-widespread pain (CnWP) are at increased risk of developing CWP, but few studies have described the nature of the development over time.We followed a random sample of 3105 participants from the population-based HUNT-3 study with five annual measurements of pain over four years. While 29% reported CWP on at least one occasion, only 7% reported it consistently on four or fsive occasions. The average annual cumulative incidence was 5% and the recovery rate was 38%. In mutual adjusted analysis, the risk of developing CWP from one year to the next was higher in subjects with chronic pain (RR=2.4; 95% CI: 1.8-3.4), two or more pain regions (RR= 3.3; 95% CI: 2.5-4.4), moderate pain or more (RR=1.8; 95% CI: 1.5-2.6) and with comorbid chronic disease (RR=1.6; 95% CI: 1.3-1.9). Developing CWP was associated with a modest concurrent change in self-reported mental and physical health. The risk of developing CWP between the fourth and fifth occasions was 80% lower for subjects without a history of CWP, compared to those with. For subjects without previous CWP, the development was associated with previously reported CnWP, but not with the number of occasions with CnWP, in analyses adjusted for sex, age and pain severity.A substantial proportion of the new cases of CWP originates from subjects floating below and above the definition for CWP over time, and thus, do not seem to involve major transitions in health.
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