Browse by Audience
The aim of this study was to determine whether post-traumatic stress disorder (PTSD) moderates treatment outcomes in Acceptance and Commitment Therapy for chronic pain.
Learn More >Celecoxib is an NSAID commonly used to treat pain conditions in humans. In addition to its blocking activity on COXs enzymes, several other targets could contribute to its analgesic activity. Here we explore the spinal antinociceptive actions of celecoxib and the potential implication of K7 channels in mediating its effects. Spinal cord in vitro preparations from hind paw-inflamed animals were used to assess the segmental sensory-motor and the early sensory processing of nociceptive information. Electrophysiological recordings of ventral roots and dorsal horn neurones were obtained and the effects of celecoxib and K7 modulators on responses to repetitive dorsal root stimulation at C-fibre intensity were assessed. Celecoxib applied at clinically relevant concentrations produced depressant effects on responses to dorsal root stimulation recorded from both ventral roots and individual dorsal horn neurones, in contrast the non-nociceptive monosynaptic reflex was unaffected. The NSAID indomethacin was devoid of effect on spinal reflexes, but further co-application of celecoxib still produced depressant effects. The depressant actions of celecoxib were abolished after K7 channel blockade and mimicked by its structural analogue dimethyl-celecoxib that lacks COX blocking activity. The present results identify K7 channels as novel central targets for celecoxib that may be relevant to its analgesic effect. This finding contributes to better understand the pharmacology of celecoxib, and reinforces both the role of K7 channels in modulating the excitability of central pain pathways and its validity as target for the design of analgesics. SIGNIFICANCE STATEMENT: N/A.
Learn More >Regular or frequent use of analgesics and acute antimigraine drugs can increase the frequency of headache, and induce the transition from episodic to chronic headache or medication overuse headache. The 1-year prevalence of this condition in the general population is between 1% and 2%. Medication overuse headache is more common in women and in people with comorbid depression, anxiety, and other chronic pain conditions. Treatment of medication overuse headache has three components. First, patients need education and counselling to reduce the intake of medication for acute headache attacks. Second, some patients benefit from drug withdrawal (discontinuation of the overused medication). Finally, preventive drug therapy and non-medical prevention might be necessary in patients at onset of treatment or in patients who do not respond to the first two steps. The optimal therapeutic approach requires validation in controlled trials.
Learn More >Preemptive analgesia encompasses different perioperative interventions that have the final aim of decreasing postoperative pain and improving recovery. Recently, peripheral analgesic effects of oxytocinergic modulation have been suggested. In this regard, we tested the potential analgesic effects of subcutaneous oxytocin (OT) infiltration in patients submitted to laparoscopic cholecystectomy.
Learn More >Back pain is the leading cause of disability worldwide and contributes to significant socioeconomic impacts worldwide. It has been hypothesized that the degenerative intervertebral disc (IVD) contributes to back pain by sensitizing nociceptive neurons innervating the IVD to stimuli that would not be painful to healthy patients; however, the inflammatory signaling networks mediating this sensitization remain poorly understood. A better understanding of the underlying mechanisms of degenerative IVD induced changes in nociception are required to improve our understanding and treatment of back pain. Towards these ends, we developed a novel in vitro model to investigate degenerative IVD induced changes in dorsal root ganglion (DRG) neuron activation by measuring DRG neuron activity following neuron seeding on human degenerative IVD tissue collected from patients undergoing surgical treatment for back pain. Lentiviral CRISPR epigenome editing vectors were built to down-regulate the inflammatory receptors TNFR1, IL1R1, and IL6st in DRG neurons in single-plex and multi-plex. Multiplex CRISPR epigenome editing of inflammatory receptors demonstrated that degenerative IVD tissue drives thermal sensitization through the simultaneous and redundant signaling of IL-6, TNF-α, and IL-1β. This work elucidates redundant signaling pathways in neuron interactions with the degenerative IVD and suggests the need for multiplex targeting of IL-6, TNF-α, and IL-1β for pain modulation in the degenerative IVD.
Learn More >The objective of this investigation was to examine the distribution of galcanezumab and a control immunoglobulin 4 antibody containing the same constant regions as galcanezumab, into peripheral and central tissues.
Learn More >Excessive prescription of opioids has become a national problem. Providers must attempt to decrease the amount of opioids prescribed while still providing patients with adequate pain relief after surgery.
Learn More >The recreational and medical use of cannabinoids has been increasing. While most studies and reviews have focused on the role of cannabinoids in the management of acute pain, no study has examined the postoperative outcomes of surgical candidates who are on cannabinoids preoperatively. This retrospective cohort study examined the impact of preoperative cannabinoid use on postoperative pain scores and pain-related outcomes in patients undergoing major orthopedic surgery.
Learn More >Chronic neuropathic pain and psychological stress interact to compromise goal-directed control over behaviour following mild psychological stress. The dorsomedial (DMS) and dorsolateral (DLS) striatum in the rat are crucial for the expression of goal-directed and habitual behaviours, respectively. This study investigated whether changes in monoamine levels in the DMS and DLS following nerve injury and psychological stress reflect these behavioural differences. Neuropathic pain was induced by a chronic constriction injury (CCI) of the sciatic nerve in Sprague-Dawley rats. Acute stress was induced using a 15 minute restraint. Behavioural flexibility was assessed using the outcome devaluation paradigm. Noradrenaline, serotonin, dopamine and associated metabolites were measured bilaterally from the DLS and DMS. In uninjured rats, restraint increased dopaminergic markers in the left and serotonergic markers in the right of both the DMS and DLS, indicating a possible left hemisphere-mediated dominance. CCI led to a slightly different lateralised effect, with a larger effect in the DMS than in the DLS. Individual differences in behavioural flexibility following CCI negatively correlated with dopaminergic markers in the right DLS, but positively correlated with these markers in the left DMS. A combination of CCI and restraint reduced behavioural flexibility, which was associated with the loss of the left/DMS dominance. These data suggest that behavioural flexibility following psychological stress or pain is associated with a left hemisphere dominance within the dorsal striatum. The loss of behavioural flexibility following the combined stressors is then associated with a transition from left to right, and DMS to DLS dominance. This article is protected by copyright. All rights reserved.
Learn More >In the midst of an epidemic of opioid abuse and overdose-related morbidity and mortality, the use of opioids remains the most common means of providing analgesia in the perioperative period. In this article, we review the risks and benefits of opioid use in preoperative, intraoperative and post-operative phases of care. Furthermore, we describe the role that surgeons and anaesthesiologists can play in reducing perioperative opioid use and mitigate their adverse effects, from both an individual and a population health perspective.
Learn More >