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Chronic low back pain (LBP) is a multifactorial disorder with complex underlying mechanisms, including associations with intervertebral disc (IVD) degeneration in some individuals. It has been demonstrated that epigenetic processes are involved in the pathology of IVD degeneration. Epigenetics refers to several mechanisms, including DNA methylation, that have the ability to change gene expression without inducing any change in the underlying DNA sequence. DNA methylation can alter the entire state of a tissue for an extended period of time and thus could potentially be harnessed for long-term pain relief. Lifestyle factors, such as physical activity, have a strong influence on epigenetic regulation. Exercise is a commonly prescribed treatment for chronic LBP, and sex-specific epigenetic adaptations in response to endurance exercise have been reported. However, whether exercise interventions that attenuate LBP are associated with epigenetic alterations in degenerating IVDs has not been evaluated.
Learn More >Low back pain covers a spectrum of different types of pain (eg, nociceptive, neuropathic and nociplastic, or non-specific) that frequently overlap. The elements comprising the lumbar spine (eg, soft tissue, vertebrae, zygapophyseal and sacroiliac joints, intervertebral discs, and neurovascular structures) are prone to different stressors, and each of these, alone or in combination, can contribute to low back pain. Due to numerous factors related to low back pain, and the low specificity of imaging and diagnostic injections, diagnostic methods for this condition continue to be a subject of controversy. The biopsychosocial model posits low back pain to be a dynamic interaction between social, psychological, and biological factors that can both predispose to and result from injury, and should be considered when devising interdisciplinary treatment plans. Prevention of low back pain is recognised as a pivotal challenge in high-risk populations to help tackle high health-care costs related to therapy and rehabilitation. To a large extent, therapy depends on pain classification, and usually starts with self-care and pharmacotherapy in combination with non-pharmacological methods, such as physical therapies and psychological treatments in appropriate patients. For refractory low back pain, a wide range of non-surgical (eg, epidural steroid injections and spinal cord stimulation for neuropathic pain, and radiofrequency ablation and intra-articular steroid injections for mechanical pain) and surgical (eg, decompression for neuropathic pain, disc replacement, and fusion for mechanical causes) treatment options are available in carefully selected patients. Most treatment options address only single, solitary causes and given the complex nature of low back pain, a multimodal interdisciplinary approach is necessary. Although globally recognised as an important health and socioeconomic challenge with an expected increase in prevalence, low back pain continues to have tremendous potential for improvement in both diagnostic and therapeutic aspects. Future research on low back pain should focus on improving the accuracy and objectivity of diagnostic assessments, and devising treatment algorithms that consider unique biological, psychological, and social factors. High-quality comparative-effectiveness and randomised controlled trials with longer follow-up periods that aim to establish the efficacy and cost-effectiveness of low back pain management are warranted.
Learn More >There are few effective treatments for acute whiplash-associated disorders (WAD). Early features of central sensitisation predict poor recovery. The effect of pregabalin on central sensitisation might prevent chronic pain after acute whiplash injury. This double blind, placebo-controlled randomised controlled trial (RCT) examined feasibility and potential effectiveness of pregabalin compared to placebo for people with acute WAD. Twenty-four participants with acute WAD (<48 hours) and at risk of poor recovery (pain ≥ 5/10) were recruited from hospital Emergency Departments in Queensland, Australia and randomly assigned by concealed allocation to either pregabalin (n=10) or placebo (n=14). Pregabalin was commenced at 75 mg bd, titrated to 300 mg bd for 4 weeks, and then weaned over 1 week. Participants were assessed at 5 weeks, 3, 6 and 12 months. Feasibility issues included recruitment difficulties and greater attrition in the placebo group. For the primary clinical outcome of neck pain intensity, attrition at 5 weeks was: pregabalin: 10%, placebo: 36%, and at 12 months was: pregabalin: 10%, placebo: 43%. Pregabalin may be more effective than placebo for the primary clinical outcome of neck pain intensity at 3 months [Mean Difference: -4.0 (95% CI -6.2 to -1.7)] on an eleven point numerical rating scale. Effects were maintained at 6 but not 12 months. There were no serious adverse events. Minor adverse events were more common in the pregabalin group. A definitive large RCT of pregabalin for acute whiplash injury is warranted. Feasibility issues would need to be addressed with modifications to the protocol.
Learn More >Migraine is a common but poorly understood sensory circuit disorder. Mouse models of familial hemiplegic migraine (FHM, a rare monogenic form of migraine with aura) show increased susceptibility to cortical spreading depression (CSD, the phenomenon that underlies migraine aura and can activate migraine headache mechanisms), allowing an opportunity to investigate the mechanisms of CSD and migraine onset. In FHM type 2 (FHM2) knock-in mice with reduced expression of astrocytic Na, K-ATPases, the reduced rate of glutamate uptake into astrocytes can account for the facilitation of CSD initiation. Here, we investigated the underlying mechanisms and show that the reduced rate of glutamate clearance in FHM2 mice results in increased amplitude and slowing of rise time and decay of the NMDA receptor (NMDAR) excitatory postsynaptic current (EPSC) elicited in layer 2/3 pyramidal cells by stimulation of neuronal afferents in somatosensory cortex slices. The relative increase in NMDAR activation in FHM2 mice is activity-dependent, being larger after high-frequency compared to low-frequency afferent activity. Inhibition of GluN1-N2B NMDARs, which hardly affected the NMDAR EPSC in wild-type mice, rescued the increased and prolonged activation of NMDARs as well as the facilitation of CSD induction and propagation in FHM2 mice. Our data suggest that the enhanced susceptibility to CSD in FHM2 is mainly due to specific activation of extrasynaptic GluN1-N2B NMDARs and point to these receptors as possible therapeutic targets for prevention of CSD and migraine.
Learn More >This study aimed to evaluate the effects of repeated bimodal transcranial direct current stimulation (tDCS) on alcohol consumption and immunohistological and neurochemical parameters in nerve-injured rats. Forty-eight adult male Wistar rats were distributed into six groups: control, neuropathic pain (NP)+sham-tDCS, NP+alcohol+sham-tDCS, alcohol+sham-tDCS, alcohol+tDCS, and NP+alcohol+tDCS. NP is induced by chronic sciatic nerve constriction (CCI). The rats were exposed to a 10% alcohol solution by voluntary consumption for 14 days. From the 16 day after surgery, bimodal tDCS was applied for 20 minutes/day for 8 days. Brain structures were collected to evaluate the number of neuropeptide Y (NPY)-positive neurons, neurites, and argyrophilic grains by immunohistochemistry, and brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), interleukin (IL)-6, and IL-10 by ELISA. Nerve-injured rats showed a progressive increase in alcohol consumption compared to the non-injured rats. In addition, there was a reduction in voluntary alcohol consumption over time induced by tDCS. Alcohol exposure, chronic pain, and tDCS treatment modulated the central NPY immunoreactivity. tDCS increased the cerebellar levels of IL-6 and IL-10, and CCI and/or tDCS reduced striatal BDNF levels. The current data suggest that tDCS could be a promising non-pharmacological adjuvant to treat patients with chronic pain who use alcohol to relieve their symptoms.
Learn More >Evidence is limited on the risk impact of body pain on future chronic disease. The present study aimed to investigate the association between body pain and chronic diseases.
Learn More >To assess the impacts of social situation changes due to the coronavirus disease 2019 (COVID-19) pandemic on headache-related disability and other symptoms in patients with migraine in Japan.
Learn More >This study was designed to explore the efficacy and feasibility of cognitive behavioural therapy(CBT) along with pregabalin and compare it with pregabalin monotherapy for the management of neuropathic pain in post-herpetic neuralgia (PHN) patients and to explore the modulation of mRNA expression of interleukin (IL)-6 and mammalian target of rapamycin-1 (mTORC1) genes in these patients.
Learn More >Although diet is an essential aspect of human health, the link between diet and pain is still not well understood. Preclinical animal research provides information to understand underlying mechanisms that allow identifying the needs for human research.
Learn More >Diminished inhibitory control of spinal nociception is one of the major culprits of chronic pain states. Restoring proper synaptic inhibition is a well-established rational therapeutic approach explored by several pharmaceutical companies. A particular challenge arises from the need for site-specific intervention to avoid deleterious side effects such as sedation, addiction, or impaired motor control, which would arise from wide-range facilitation of inhibition. Specific targeting of glycinergic inhibition, which dominates in the spinal cord and parts of the hindbrain, may help reduce these side effects. Selective targeting of the α3 subtype of glycine receptors (GlyRs), which is highly enriched in the superficial layers of the spinal dorsal horn, a key site of nociceptive processing, may help to further narrow down pharmacological intervention on the nociceptive system and increase tolerability. This review provides an update on the physiological properties and functions of α3 subtype GlyRs and on the present state of related drug discovery programs.
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