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Intra-amygdala infusion of zeta inhibitory peptide attenuates neuropathic pain but not inflammatory pain in adult rats.

Protein kinase Mζ (PKMζ), a typical brain-specific PKC isoform, has been shown to be critical in the maintenance of long-term potentiation and memory storage. Zeta inhibitory peptide (ZIP), a peptide with selective inhibition of PKMζ, has been used in relieving experimental neuropathic pain and disrupting memory. The aim of this study was to investigate the effects of intra-amygdalar infusion of ZIP on neuropathic pain induced by chronic constriction injury (CCI), and inflammatory pain induced by complete Freund's adjuvant (CFA) in adult rats.

A Pilot Randomized Controlled Trial Comparing Mindfulness Meditation, Cognitive Therapy, and Mindfulness-Based Cognitive Therapy for Chronic Low Back Pain.

This pilot trial compared the feasibility, tolerability, acceptability, and effects of group-delivered mindfulness meditation (MM), cognitive therapy (CT), and mindfulness-based cognitive therapy (MBCT) for chronic low back pain (CLBP).

Endogenous Pain Modulation Assessed with Offset Analgesia Is Not impaired in Chronic Temporomandibular Disorders Pain Patients.

Abnormal endogenous pain modulation (EPM) was suggested as a pathophysiological characteristic of chronic pain. EPM has been investigated using psychophysical tests for pain facilitation and inhibition such as temporal summation of pain and conditioned pain modulation, respectively. Another psychophysical test for pain inhibition is offset analgesia (OA), where small variations in noxious stimulus intensity over time elicit a disproportionately large analgesic response. OA has been investigated in patients with mixed pain conditions, but not in chronic temporomandibular disorders (TMD) patients.

CD11b+ cells markedly express the itch cytokine interleukin 31 in polymorphic light eruption.

Itch is one of the cardinal symptoms of polymorphic light eruption (PLE), the most common form of photodermatosis known to be mediated immunologically. Indeed, very often itch precedes the skin lesions of the condition or may be even the only symptom in PLE, which sometimes is aggravated to a burning sensation. There have been reports of a variant called PLE sine eruption, with intense pruritus on the sun-exposed parts without any visible skin changes. This article is protected by copyright. All rights reserved.

Epigenomic signatures underpin the axonal regenerative ability of dorsal root ganglia sensory neurons.

Axonal injury results in regenerative success or failure, depending on whether the axon lies in the peripheral or the CNS, respectively. The present study addresses whether epigenetic signatures in dorsal root ganglia discriminate between regenerative and non-regenerative axonal injury. Chromatin immunoprecipitation for the histone 3 (H3) post-translational modifications H3K9ac, H3K27ac and H3K27me3; an assay for transposase-accessible chromatin; and RNA sequencing were performed in dorsal root ganglia after sciatic nerve or dorsal column axotomy. Distinct histone acetylation and chromatin accessibility signatures correlated with gene expression after peripheral, but not central, axonal injury. DNA-footprinting analyses revealed new transcriptional regulators associated with regenerative ability. Machine-learning algorithms inferred the direction of most of the gene expression changes. Neuronal conditional deletion of the chromatin remodeler CCCTC-binding factor impaired nerve regeneration, implicating chromatin organization in the regenerative competence. Altogether, the present study offers the first epigenomic map providing insight into the transcriptional response to injury and the differential regenerative ability of sensory neurons.

Vestibular Migraine.

The term vestibular migraine designates recurrent vertigo that is caused by migraine. Vestibular migraine presents with episodes of spontaneous or positional vertigo lasting seconds to days that are accompanied by migraine symptoms. Because headache is often absent during acute attacks, other migraine features have to be identified by thorough history taking. In contrast, vestibular testing serves mainly for the exclusion of other diagnoses. Treatment still lacks solid evidence. It is targeted at the underlying migraine and comprises explanation and reassurance, lifestyle modifications, and drugs.

VA/DoD Clinical Practice Guideline: Diagnosis and Treatment of Low Back Pain.

In September 2017, the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) approved the joint Clinical Practice Guideline (CPG) for Diagnosis and Management of Low Back Pain. This CPG was intended to provide healthcare providers a framework by which to evaluate, treat, and manage patients with low back pain (LBP).

Streptozotocin-induced diabetic neuropathic pain is associated with potentiated calcium-permeable AMPA receptor activity in the spinal cord.

Neuronal hyperactivity in the spinal dorsal horn can amplify nociceptive input in diabetic neuropathic pain. The glutamate N-methyl-D-aspartate and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (NMDA receptors and AMPA receptors, respectively) are involved in spinal nociceptive transmission. However, it is unclear whether painful diabetic neuropathy is associated with changes in the activity of synaptic NMDA receptors and AMPA receptors in spinal dorsal horn neurons. AMPA receptors lacking GluA2 are Ca2+ permeable (CP-AMPA receptors), and their currents display characteristic inward rectification. In this study, we showed that evoked excitatory postsynaptic currents (EPSCs) exhibited inward rectification in spinal dorsal neurons in diabetic rats induced by streptozotocin. Interestingly, presynaptic and postsynaptic NMDA receptor activity in the spinal dorsal horn was similar in diabetic and control rats. In the dorsal spinal cord, the membrane GluA2 protein level was significantly less in diabetic than in control rats, whereas the cytosolic GluA2 level was greater in diabetic than in control rats. In contrast, the GluA1 subunit levels in the plasma membrane and cytosol did not differ between the two groups. Blocking CP-AMPA receptors significantly reduced the amplitude of EPSCs of dorsal horn neurons in diabetic but not in control rats. Furthermore, blocking spinal CP-AMPA receptors reduced pain hypersensitivity in diabetic rats but had no effect on nociception in control rats. Our study suggests that diabetic neuropathy augments CP-AMPA receptor activity in the spinal dorsal horn by causing intracellular retention of GluA2 and impairing GluA2 membrane trafficking. Increased prevalence of spinal CP-AMPA receptors sustains diabetic neuropathic pain. SIGNIFICANCE STATEMENT: This study demonstrates that the prevalence of synaptic calcium permeable-AMPA receptors is increased in the spinal dorsal horn, which mediates pain hypersensitivity in diabetic neuropathy. Thus, calcium permeable-AMPA receptors play an important role in glutamatergic synaptic plasticity in the spinal cord in painful diabetic neuropathy. This new knowledge improves our understanding of the mechanisms involved in central sensitization associated with diabetic neuropathic pain and suggest that calcium permeable-AMPA receptors are an alternative therapeutic target for treating this chronic pain condition.

Cannabinoids versus placebo or no intervention for pain: protocol for a systematic review with meta-analysis and trial sequential analysis.

Pain is a frequent clinical symptom with significant impact on the patient's well-being. Therefore, adequate pain management is of utmost importance. While cannabinoids have become a more popular alternative to traditional types of pain medication among patients, the quality of evidence supporting the use of cannabinoids has been questioned. The beneficial and harmful effects of cannabinoids in patients with pain is unknown. Accordingly, we aim to assess the efficacy, tolerability and safety of cannabinoids (herbal, plant-derived extracts and synthetic) compared with placebo or no intervention for any type of pain.

The effect of chronic, non-specific low back pain on superficial lumbar muscle activity: a protocol for a systematic review and meta-analysis.

Chronic, non-specific low back pain is a major global cause of disability. One factor which might potentially contribute to ongoing pain is maladaptive variation in the level of activity in the lumbar musculature. Several studies have investigated this activity using surface electromyography, in varied muscles and during a number of functional activities. Due to differences in the applied methodology, the results have been difficult to compare, and previous reviews have been limited in scope. In this protocol, we aim to perform a comprehensive review of the effect of chronic low back pain on lumbar muscle activity.

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