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The role of neurotransmitters and neuromodulators in the pathogenesis of cluster headache: a review.
The pathogenesis underlying cluster headache remains an unresolved issue. Although both the autonomic system and the hypothalamus play a central role, the modality of their involvement remains largely unknown. It is, also, unknown why the duration of the pain attacks is so brief and why their onset and termination are abrupt and extremely painful. This review summarizes the evidence to date accumulated in favor of a possible role of anomalies in the metabolism of tyrosine, tryptophan, and arginine in these unresolved issues.
Learn More >Persistent breast pain (PBP) is prevalent among breast cancer survivors and has powerful negative psychological consequences. The present study provided a first test of the hypothesis that: (a) pain catastrophizing, (b) heightened perceived risk of cancer, and (c) worry that pain indicates cancer may be independent mediating links between breast cancer survivors' experiences of PBP and heightened emotional distress.
Learn More >The orphan nuclear receptors REV-ERBα and REV-ERBβ (REV-ERBs) are crucial in the regulation of inflammatory-related gene transcription in astroglioma cells, but their role in nociceptive transduction has yet to be elaborated. Spinal dorsal horn astrocytes contribute to the maintenance of chronic pain. Treatment of cultured spinal astrocytes with specific REV-ERBs agonists SR9009 or GSK4112 significantly prevented lipopolysaccharide (LPS)-induced mRNA upregulation of pronociceptive molecules interleukin-1β (IL-1β) mRNA, interleukin-6 (IL-6) mRNA and matrix metalloprotease-9 (MMP-9) mRNA, but not CCL2 mRNA expression. Treatment with SR9009 also blocked tumor necrosis factor-induced IL-1β mRNA, IL-6 mRNA and MMP-9 mRNA. In addition, treatment with SR9009 significantly blocked LPS-induced upregulation of IL-1β protein, IL-6 protein and MMP-9 activity. The inhibitory effects of SR9009 on LPS-induced expression of pronociceptive molecules were blocked by knockdown of REV-ERBs expression with short interference RNA, confirming that SR9009 exerts its effect through REV-ERBs. Intrathecal LPS treatment in male mice induces hind paw mechanical hypersensitivity, and upregulation of IL-1β mRNA, IL-6 mRNA and glial fibrillary acidic protein (GFAP) expression in spinal dorsal horn. Intrathecal pretreatment of SR9009 prevented the onset of LPS-induced mechanical hypersensitivity, cytokine expression and GFAP expression. Intrathecal injection of SR9009 also ameliorated mechanical hypersensitivity during the maintenance phase of complete Freund's adjuvant-induced inflammatory pain and partial sciatic nerve ligation-, paclitaxel-, and streptozotocin-induced neuropathy in mice. The current findings suggest that spinal astrocytic REV-ERBs could be critical in the regulation of nociceptive transduction through downregulation of pronociceptive molecule expression. Thus, spinal REV-ERBs could be an effective therapeutic target in the treatment of chronic pain.
Learn More >Neuropathic pain is caused by a lesion or dysfunction in the nervous system, and it may arise from illness, be drug-induced or caused by toxin exposure. Since the discovery of two G-protein-coupled cannabinoid receptors (CB and CB) nearly three decades ago, there has been a rapid expansion in our understanding of cannabinoid pharmacology. This is currently one of the most active fields of neuropharmacology, and interest has emerged in developing cannabinoids and other small molecule modulators of CB and CB as therapeutics for neuropathic pain. This short review article provides an overview of the chemotypes currently under investigation for the development of novel neuropathic pain treatments targeting CB receptors.
Learn More >Musculoskeletal pain is a prevalent health challenge for all age groups worldwide, but most notably in older adults. Social isolation is the consequence of a decrease in social network size with a reduction in the number of social contacts. Loneliness is the psychological embodiment of social isolation and represents an individual's perception of dissatisfaction in the quality or quantity of their social contacts. This study aims to determine whether a relationship exists between musculoskeletal pain and social isolation and loneliness.
Learn More >The goal of this narrative review is to provide an overview of migraine pathophysiology, with an emphasis on the role of calcitonin gene-related peptide (CGRP) within the context of the trigeminovascular system.
Learn More >To optimally select chronic pain patients for different treatments, as it is of interest to identify patient characteristics that might moderate treatment effect. Our aim was to evaluate the impact of possible moderators on the effect of acupuncture treatment using a large data set.
Learn More >Nerve growth factor (NGF) has emerged as a key driver of pain in osteoarthritis (OA) and antibodies to NGF are potent analgesics in human disease. Here, we validate a novel vaccine strategy to generate anti-NGF antibodies for reversal of pain behaviour in a surgical model of OA.
Learn More >To assess the characteristics of breakthrough cancer pain (BTcP) in patients with abdominal cancer pain, and the eventual factors associated with its presentation.
Learn More >The distinctive experience of pain, beyond mere processing of nociceptive inputs, is much debated in psychology and neuroscience. One aspect of perceptual experience is captured by metacognition-the ability to monitor and evaluate one's own mental processes. We investigated confidence in judgements about nociceptive pain (i.e. pain that arises from the activation of nociceptors by a noxious stimulus) to determine whether metacognitive processes contribute to the distinctiveness of the pain experience. Our participants made intensity judgements about noxious heat, innocuous warmth, and visual contrast (first-order, perceptual decisions) and rated their confidence in those judgements (second-order, metacognitive decisions). First-order task performance between modalities was balanced using adaptive staircase procedures. For each modality, we quantified metacognitive efficiency (meta-d'/d')-the degree to which participants' confidence reports were informed by the same evidence that contributed to their perceptual judgements-and metacognitive bias (mean confidence)-the participant's tendency to report higher or lower confidence overall. We found no overall differences in metacognitive efficiency or mean confidence between modalities. Mean confidence ratings were highly correlated between all three tasks, reflecting stable inter-individual variability in metacognitive bias. However, metacognitive efficiency for pain varied independently of metacognitive efficiency for warmth and visual perception. That is, those participants who had higher metacognitive efficiency in the visual task also tended to have higher metacognitive efficiency in the warmth task, but not necessarily in the pain task. We thus suggest that some distinctive and idiosyncratic aspects of the pain experience may stem from additional variability at a metacognitive level. We further speculate that this additional variability may arise from the affective or arousal aspects of pain.
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