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Spinal cord stimulation has been an established treatment for chronic back and leg pain for more than 50 years; however, outcomes are variable and unpredictable, and objective evidence of the mechanism of action is needed. A novel spinal cord stimulation system provides the first in vivo, real-time, continuous objective measure of spinal cord activation in response to therapy via recorded evoked compound action potentials (ECAPs) in patients during daily use. These ECAPs are also used to optimise programming and deliver closed-loop spinal cord stimulation by adjusting the stimulation current to maintain activation within patients' therapeutic window. We aimed to examine pain relief and the extent of spinal cord activation with ECAP-controlled closed-loop versus fixed-output, open-loop spinal cord stimulation for the treatment of chronic back and leg pain.
Learn More >The aim of this systematic review was to compile the latest evidence to assess the effectiveness of nonsteroidal anti-inflammatory drug(s) (NSAID) in patients with temporomandibular joint disorders (TMDs) in relieving pain. TMDs are a group of musculoskeletal disorders that affect the temporomandibular joint and/or masticatory muscles.
Learn More >Agonists at the δ opioid receptor are known to be potent anti-hyperalgesics in chronic pain models and to be effective in models of anxiety and depression. However, some δ opioid agonists have pro-convulsant properties whilst tolerance to the therapeutic effects can develop. Previous evidence indicates that different agonists acting at the δ opioid receptor differentially engage signalling and regulatory pathways with significant effects on behavioural outcomes. As such, interest is now growing in the development of biased agonists as a potential means to target specific signalling pathways and potentially improve the therapeutic profile of δ opioid agonists. Here we report on PN6047 (3-[[4-(dimethylcarbamoyl)phenyl]-[1-thiazol-5-ylmethyl)-4-piperidylidene]methyl]benzamide) a novel G protein-biased and selective δ opioid agonist. In cell based assays PN6047 fully engages G protein signalling but is a partial agonist in both the arrestin recruitment and internalisation assays. PN6047 is effective in rodent models of chronic pain but shows no detectable analgesic tolerance following prolonged treatment. In addition, PN6047 exhibited antidepressant-like activity in the forced swim test and importantly, the drug had no effect on chemically induced seizures. PN6047 did not exhibit reward-like properties in the conditioned place preference test or induce respiratory depression. Thus, δ opioid ligands with limited arrestin signalling such as PN6047 may be therapeutically beneficial in the treatment of chronic pain states. SIGNIFICANCE STATEMENT: PN6047 is a selective, G protein-biased δ opioid agonist with efficacy in preclinical models of chronic pain. No analgesic tolerance was observed after prolonged treatment and PN6047 does not display pro-convulsant activity or other opioid-mediated adverse effects. Our data suggest that δ opioid ligands with limited arrestin signalling will be beneficial in the treatment of chronic pain.
Learn More >We investigated the efficacy of duloxetine on hyperalgesia, histopathological and radiographic findings, pain-related sensory innervation of dorsal-root ganglia (DRG), and spinal changes in a rat model of induced hip osteoarthritis (OA). The right hip joints of male Sprague-Dawley rats (n = 6 rats/group) in the Sham group were injected with 25 μL of sterile saline and 25 μL of sterile saline with 2 mg of monosodium iodoacetate (MIA) were injected to the MIA + Vehicle and MIA + Duloxetine groups. We injected duloxetine 20 mg/kg intraperitoneally in the MIA + Duloxetine group 28 days after injection, whereas rats in the MIA + Vehicle group were injected with 0.5 mL of 20% dimethyl sulfoxide. We assessed hyperalgesia, histopathological changes, immunoreactive (-ir) neurons for calcitonin gene-related peptide and activating transcription factor 3 in DRG, and immunoreactive neurons for ionized-calcium-binding adaptor molecule 1 (Iba1) in the dorsal horn of the spinal cord. MIA administration into the hip joint let to mechanical hyperalgesia of the ipsilateral hind paw (p < 0.05). A single injection of duloxetine significantly attenuated it in induced hip OA (p < 0.05) and suppressed the number of Iba1-ir microglia of the ipsilateral dorsal horn (p < 0.05). These results suggest that a single injection of duloxetine suppressed mechanical hyperalgesia and may influence the expression of Iba1 in the microglia of the ipsilateral dorsal horn in the MIA-induced hip OA. This finding implies the inhibitory effects of duloxetine against neuropathic pain, which may lead to a change of microglial activities. This article is protected by copyright. All rights reserved.
Learn More >To investigate the effects of the inclusion of neural mobilization into a motor control exercise program on pain, related-disability, neuropathic symptoms, straight leg raise (SLR), and pressure pain threshold (PPT) in lumbar radiculopathy.
Learn More >Using experimental, yet realistic, headache calendars, this laboratory study evaluated the ability of individuals to identify the degree of association between triggers and headaches.
Learn More >High-quality evidence on how to improve palliative care in nursing homes is lacking.
Learn More >Patients with radicular low back pain (radicular LBP, sciatica) frequently describe their pain as "shooting" or "radiating". The dictionary meaning of these words implies rapid movement, and indeed, many sufferers report feeling pain moving rapidly from the lower back or buttock into the leg. But others do not. Moreover, the sensation of movement is paradoxical; it is neither predicted nor accounted for by current ideas about the pathophysiology of radicular LBP. We have employed a structured questionnaire to evaluate the sensory qualities associated with "shooting" and "radiating" in 155 patients, 98 with radicular LBP and 57 with trigeminal neuralgia (TN), a second chronic pain condition in which shooting/radiating are experienced. Results indicated a spectrum of different sensations in different people. While many sciatica patients reported rapid downward movement of their pain, even more reported downward expansion of the area of pain, some reported upward movement and for some there was no spatial dynamic at all. The velocity of movement or expansion was also variable. By cross-referencing sensations experienced in the sciatica and TN cohorts with known signal processing modes in the somatosensory system, we propose testable hypotheses concerning the pathophysiology of the various vectorial sensations reported, their direction and velocity, and the structures in which they are generated. Systematic evaluation of qualitative features of "shooting" and "radiating" pain at the time of diagnosis can shed light on the pain mechanism in the individual patient and perhaps contribute to a better therapeutic outcomes.
Learn More >Chronic non-specific low back pain (CLBP) is a common clinical condition that has impacts at both the individual and societal level. Pain intensity is a primary outcome used in clinical practice to quantify the severity of CLBP and the efficacy of its treatment, however, pain is a subjective experience that is impacted by a multitude of factors. Moreover, differences in effect sizes for pain intensity are not observed between common conservative treatments, such as spinal manipulative therapy, cognitive behavioural therapy, acupuncture and exercise training. As pain science evolves, the biopsychosocial model is gaining interest in its application for CLBP management. The aim of this paper is to discuss our current scientific understanding of pain and present why additional factors should be considered in conservative CLBP management. In addition to pain intensity, we recommend that clinicians should consider assessing the multidimensional nature of CLBP by including physical (disability, muscular strength and endurance, performance in activities of daily living and body composition), psychological (kinesiophobia, fear-avoidance, pain catastrophizing, pain self-efficacy, depression, anxiety and sleep quality), social (social functioning and work absenteeism) and health-related quality of life measures, depending on what is deemed relevant for each individual. This review also provides practical recommendations to clinicians for the assessment of outcomes beyond pain intensity, including information on how large a change must be for it to be considered 'real' in an individual patient. This information can guide treatment selection when working with an individual with CLBP.
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