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Chronic pain is highly comorbid with affective disorders, including major depressive disorder. A core feature of major depressive disorder is a loss of interest in previously rewarding activities. Major depressive disorder is also associated with negative affective biases where cognitive processes are modulated by the affective state. Previous work from our laboratory has shown that reward-related learning and memory is impaired in rodent models of depression generated through a variety of different manipulations. This study investigated different aspects of reward-related behaviour in a rodent model of chronic pain, the partial saphenous nerve injury (PSNI). Using our reward-learning assay, an impairment in reward learning was observed with no difference in sucrose preference, consistent with a lack of effect on reward sensitivity and similar to the effects seen in depression models. In a successive negative contrast task, chronic pain was not associated with changes in motivation for reward either under normal conditions or when reward was devalued although both sham and PSNI groups exhibited the expected negative contrast effect. In the affective bias test, PSNI rats developed a positive affective bias when treated with gabapentin, an effect not seen in the controls suggesting an association with the antinociceptive effects of the drug inducing a relatively more positive affective state. Together, these data suggest that there are changes in reward-related cognition in this chronic pain model consistent with previous findings in rodent models of depression. The effects seen with gabapentin suggest that pain-associated negative affective state may be remediated by this atypical analgesic.
Learn More >It is common for youth to engage in sport and unfortunately also common for chronic pain to emerge in childhood. The convergence of chronic pain and sports participation in youth has not been extensively studied.
Learn More >Sustained neuropathic pain from injury or inflammation remains a major burden for society. Rodent pain models have informed some cellular mechanisms increasing neuronal excitability within the spinal cord and primary somatosensory cortex (S1), but how activity patterns within these circuits change during pain remains unclear. We have applied multiphoton in vivo imaging and holographic stimulation to examine single S1 neuron activity patterns and connectivity during sustained pain. Following pain induction, there is an increase in synchronized neuronal activity and connectivity within S1, indicating the formation of pain circuits. Artificially increasing neuronal activity and synchrony using DREADDs reduced pain thresholds. The expression of N-type voltage-dependent Ca channel subunits in S1 was increased after pain induction, and locally blocking these channels reduced both the synchrony and allodynia associated with inflammatory pain. Targeting these S1 pain circuits, via inhibiting N-type Ca channels or other approaches, may provide ways to reduce inflammatory pain.
Learn More >Migraine is a neurovascular disorder that is three times more prevalent in women than in men and represents a large socio-economic burden. Therefore, the development of new preventive medications is an urgent matter. Currently, calcitonin gene-related peptide (CGRP), a neuropeptide released from trigeminal fibres, is an important target for migraine treatment. Accordingly, antibodies directed against CGRP or its receptor, as well as small-molecule CGRP receptor antagonists, have been developed for the prophylactic and acute treatment of migraine. Results from clinical phase III trials show a significant decrease in migraine days and relatively mild side-effects. However, CGRP is not only present in the trigeminal nerve, but it is also abundant in perivascular nerve fibres. Moreover, CGRP levels and hormones vary between sexes and during different life stages, and hormones affect CGRP, with a seemingly greater role for CGRP in females. In this review we discuss whether these aspects could be associated with differences in response and efficacy of drugs interfering with the CGRP pathway. Furthermore, CGRP has been described as playing a protective role in ischemic events, and CGRP seems to play a larger role in cardiac ischemic events in female patients. As cardiovascular risk is increased in female migraine patients and also increases significantly in females after menopause, further research into the risk of blocking CGRP in these patients is needed.
Learn More >Understanding which pediatric patients seek opioid refills is crucial as prescription opioid use in childhood is associated with an increased risk of future opioid misuse. Orthopaedic surgeons are optimally positioned to lead the charge in addressing the opioid epidemic. The aim of this study was to describe the incidence of and risk factors associated with requiring opioid refills after pediatric orthopaedic surgery in children.
Learn More >Insulin resistance (IR) is a pathological condition in which cells fail to respond normally to insulin. IR has been associated with multiple conditions, including chronic pain. Fibromyalgia (FM) is one of the common generalized chronic painful conditions with an incidence rate affecting 3% to 6% of the population. Substantial interest and investigation into FM continue to generate many hypotheses.The relationship between IR and FM has not been explored. IR is known to cause abnormalities in the cerebral microvasculature, leading to focal hypoperfusion. IR also has been shown to cause cognitive impairment in FM patients, as in parkinsonism. As demonstrated by advanced imaging methods, similar brain perfusion abnormalities occur in the brain of patients with FM as with IR.
Learn More >Posttraumatic headache (PTH) is a common debilitating condition arising from head injury and is highly prevalent among military service members and veterans with traumatic brain injury (TBI). Diagnosis and treatment for PTH is still evolving, and surprisingly little is known about the putative mechanisms that drive these headaches. This manuscript describes the design of a randomized clinical trial of two nonpharmacological (i.e., behavioral) interventions for posttraumatic headache. Design of this trial required careful consideration of PTH diagnosis and inclusion criteria, which was challenging due to the lack of standard clinical characteristics in PTH unique from other types of headaches. The treatments under study differed in clinical focus and dose (i.e., number of treatment sessions), but the trial was designed to balance the treatments as well as possible. Finally, while the primary endpoints for pain research can vary from assessments of pain intensity to objective and subjective functional measures, this trial of PTH interventions chose carefully to establish clinically relevant endpoints and to maximize the opportunity to detect significant differences between groups with two primary outcomes. All these issues are discussed in this manuscript.
Learn More >Although conventional pain relief therapeutics have centered around mu-opioid agonists, these drugs are limited by adverse side effects, including respiratory depression and addiction potential. The ongoing opioid epidemic has galvanized research into novel analgesic therapies with more favorable profiles. New pharmacologic agents have been developed to target neuronal pathways involved in pain sensation. Certain receptors have been recognized to mediate nociceptive transmission, central sensitization, and the development of chronic pain states.
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