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Chronic pain is one of the most common and challenging symptoms in fibromyalgia (FM). Currently, self-reported pain is the main criterion used by clinicians assessing patients with pain. However, it is subjective, and multiple factors can affect pain levels. In this study, we investigated the neural correlates of FM pain using conditioned pain modulation (CPM), electroencephalography (EEG), and transcranial magnetic stimulation (TMS).
The contributions of intervertebral disc disease and subject-specific covariates to systemic inflammation in low back pain are unknown. We examined the effects of symptomatic disc herniation (DH) and MRI herniation severity on serum cytokine levels in clinical subjects.
Remote electrical neuromodulation (REN) is a novel acute treatment of migraine. Upper arm peripheral nerves are stimulated to induce conditioned pain modulation (CPM)-an endogenous analgesic mechanism in which conditioning stimulation inhibits pain in remote body regions. The REN device (Nerivio, Theranica Bio-Electronics LTD., Israel) is FDA-authorized for acute treatment of migraine in adults who do not have chronic migraine. The current study assessed the consistency of response over multiple migraine attacks in people with chronic migraine who are typically characterized with severe pain intensity, high disability, and less robust response to triptans.
Tapentadol is a dual-acting mu-opioid receptor agonist and noradrenaline reuptake inhibitor with non-inferior analgesic efficacy to oxycodone and better gastrointestinal tolerability than full mu-opioid receptor agonists. Tapentadol is approved for cancer pain in Japan; however, real-world evidence on tapentadol's effectiveness and safety for cancer-related pain in Japan is limited.
Transcranial direct current stimulation (tDCS) has been used to reduce pain in range of chronic pain states. The aim of this review is to evaluate the effectiveness of tDCS on pain reduction and related disability in patients with non-specific chronic low back pain (CLBP). A computer-based systematic literature search was performed in five databases according to PRISMA guidelines. Randomized controlled trials (RCTs) that assessed the effects of tDCS on pain and related disability in patients with non-specific CLBP were included. Modified Jadad scale and Cochrane's risk of bias assessment were used to determine the studies' quality and risk of bias. Meta-analyses were performed by calculating the standardized mean difference (SMD) at 95% confidence interval (CI). Nine RCTs (411 participants) were included in the systematic review according to inclusion criteria, while only five studies could be included in the meta-analysis. The primary motor cortex (M1) was the main stimulated target. The meta-analysis showed non-significant effect of multiple sessions of tDCS over M1 on pain reduction and disability post-treatment respectively, (SMD = 0.378; 95% CI = - 0.264-1.020; P = 0.249), (SMD = 0.143; 95% CI = - 0.214-0.499; P = 0.434). No significant adverse events were reported. The current results do not support the clinical use of tDCS for the reduction of pain and related disability in non-specific CLBP. However, the limited number of available evidence limits our conclusions on the effectiveness of these approaches.
Offset analgesia identifies impaired endogenous pain modulation in pediatric chronic pain disorders.
Offset analgesia (OA), a psychophysical test of endogenous pain inhibition, is diminished in many adult chronic pain disorders but OA has not been investigated in youth with chronic pain disorders. The present study assessed OA responses in 30 youth with chronic primary and secondary pain disorders and 32 healthy controls. The OA, control and constant thermal tests were evoked with an individualized noxious heat stimulus of approximately 50/100 mm on a visual analog scale followed by 1°C offset temperature. This study also examined the association of OA responses with two self-report measures of pain sensitivity, the Central Sensitization Inventory (CSI) and Pain Sensitivity Questionnaire (PSQ). Patients exhibited diminished capacity to activate OA with a reduction in ΔeVASc of 53 ± 29% vs. controls 74 ± 24% (P = 0.003) even after multivariate regression adjusting for age, sex and body mass index. Patients also showed decreased ability to habituate to a constant noxious heat stimulus compared to controls (P = 0.021). CSI scores showed excellent predictive accuracy in differentiating patients from controls (AUC= 0.95; 95% CI: 0.91, 0.99) and CSI score ≥ 30 was identified as an optimal cut-off value. PSQ scores did not differentiate patients from controls nor correlate with OA. In this study 60% of youth with chronic pain showed reduced capacity for endogenous pain inhibition.
Cancer invading into nerves, termed perineural invasion (PNI), is associated with pain. Here we show that oral cancer patients with PNI report greater spontaneous pain and mechanical allodynia compared with patients without PNI, suggesting unique mechanisms drive PNI-induced pain. We studied the impact of PNI on peripheral nerve physiology and anatomy using a murine sciatic nerve PNI model. Mice with PNI exhibited spontaneous nociception and mechanical allodynia. PNI induced afterdischarge in A high threshold mechanoreceptors (AHTMRs), mechanical sensitization (i.e., decreased mechanical thresholds) in both A and C HTMRs, and mechanical desensitization in low threshold mechanoreceptors (LTMRs). PNI resulted in nerve damage, including axon loss, myelin damage, and axon degeneration. Electrophysiological evidence of nerve injury included decreased conduction velocity, and increased percentage of both mechanically-insensitive and electrically-unexcitable neurons. We conclude that PNI-induced pain is driven by nerve injury and peripheral sensitization in HTMRs.
Chronic widespread pain conditions are more prevalent in women than men suggesting a role for gonadal hormones in the observed differences. Previously, we showed female mice, compared to male, develop widespread, more severe, and longer duration hyperalgesia in a model of activity-induced muscle pain. We hypothesized testosterone protects males from developing the female pain phenotype. We tested if orchiectomy of males prior to induction of an activity-induced pain model produced a female phenotype and if testosterone administration produced a male phenotype in females. Orchiectomy produced longer lasting, more widespread hyperalgesia, similar to females. Administration of testosterone to females or orchiectomized males produced unilateral, shorter lasting hyperalgesia. Prior studies show that the serotonin transporter (SERT) is increased in the nucleus raphe magnus (NRM) in models of chronic pain, and that blockade of SERT in the NRM reduces hyperalgesia. We examined potential sex differences in the distribution of SERT across brain sites involved in nociceptive processing using immunohistochemistry. A sex difference in SERT was found in the NRM in the activity-induced pain model; females had greater SERT-immunoreactivity than males. This suggests testosterone protects against development of widespread, long-lasting muscle pain and that alterations in SERT may underlie the sex differences.
Increased excitability of primary sensory neurons after peripheral nerve injury may cause hyperalgesia and allodynia. Dorsal root ganglion field stimulation (GFS) is effective in relieving clinical pain associated with nerve injury and neuropathic pain in animal models. However, its mechanism has not been determined. We examined effects of GFS on transmission of action potentials (APs) from the peripheral to central processes by in vivo single unit recording from lumbar dorsal roots in sham injured rats and rats with tibial nerve injury (TNI) in fiber types defined by conduction velocity. Transmission of APs directly generated by GFS (20Hz) in C-type units progressively abated over 20s, whereas GFS-induced Aβ activity persisted unabated, while Aδ showed an intermediate pattern. Activity generated peripherally by electrical stimulation of the sciatic nerve and punctate mechanical stimulation of the receptive field (glabrous skin) was likewise fully blocked by GFS within 20s in C-type units, whereas Aβ units were minimally affected and a subpopulation of Aδ units were blocked. After tibial nerve injury, the threshold to induce AP firing by punctate mechanical stimulation (von Frey) was reduced, which was reversed to normal during GFS. These results also suggest that C-type fibers, not Aβ, mainly contribute to mechanical and thermal hypersensitivity (von Frey, bush, acetone) after injury. GFS produces use-dependent blocking of afferent AP trains, consistent with enhanced filtering of APs at the sensory neuron T-junction, particularly in nociceptive units.
To quantify preferences for attributes of potential analgesic treatments for moderate-to-severe pain associated with osteoarthritis (OA) and/or chronic low back pain (CLBP) as relevant to injectable nerve growth factor (NGF)-inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), and opioids.