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Migraine patients want acute treatment to provide complete relief of the migraine attack within 30 minutes. Traditionally, "speed of onset of effect" is evaluated by estimating the time-point for first statistical separation of drug and placebo. The estimated onset of effect can be a few percent difference of patients being pain free in very large randomised, controlled trials. This difference, however, can be clinically irrelevant.
Learn More >Pharmacological management of migraine can be ineffective for some patients. We previously demonstrated that exposure to green light resulted in antinociception and reversal of thermal and mechanical hypersensitivity in rodent pain models. Given the safety of green light emitting diodes, we evaluated green light as a potential therapy in patients with episodic or chronic migraine.
Learn More >Increasing evidence suggests that vasoactive neuropeptides such as pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38), substance P, calcitonin gene-related peptide, and vasoactive intestinal peptide are involved in the pathophysiology of migraine in adults, but their role in pediatric migraineurs remains unclear. We prospectively investigated plasma levels of these vasoactive neuropeptides in pediatric migraine patients without aura and compared the results with those of age-matched healthy controls.
Learn More >Pain on the body surface can accompany disorders in the deep tissue or internal organs. However, the anatomical and physiological mechanisms are obscure. Here, we provided direct evidence of axon bifurcation in primary C-nociceptive neurons that innervate both the skin and a visceral organ. Double-labeled dorsal root ganglion (DRG) neurons and Evans blue extravasation were observed in 3 types of chemically-induced visceral inflammation (colitis, urocystitis, and acute gastritis) rat models. In the colitis model, mechanical hypersensitivity and spontaneous activity were recorded in vivo from double-labeled C-nociceptive neurons in S1 or L6 DRGs. These neurons showed significantly enhanced responses to both somatic stimulation and colorectal distension. Our findings suggest that the branching of C-nociceptor axons contribute to cutaneous hypersensitivity in visceral inflammation. Cutaneous hypersensitivity on certain locations of the body surface might serve as an indicator of pathological conditions in the corresponding visceral organ.
Learn More >Neuropathic pain (NP) can occur after peripheral nerve injury (PNI), and it can be converted into a maladaptive, detrimental phenotype that causes a long-term state of pain hypersensitivity. In the last decade, the discovery that dysfunctional microglia evoke pain, called "microgliopathic pain," has challenged traditional neuronal views of "pain" and has been extensively explored. Recent studies have shown that microRNAs (miRNAs) can act as activators or inhibitors of spinal microglia in NP conditions. We first briefly review spinal microglial activation in NP. We then comprehensively describe miRNA expression changes and their potential mechanisms in the response of microglia to nerve injury. We summarize the roles of the following two representative miRNAs: miR-124, which reverses NP by keeping microglia quiescent, and miR-155, which promotes NP following microglial activation. Finally, we focused on the therapeutic potential of microglial miRNAs in NP. The findings we summarized may be essential tools for basic research and clinical treatment of NP.
Learn More >To evaluate the presence and characterization of chemotherapy-induced neuropathy (CIPN) and neuropathic pain 5 years after adjuvant chemotherapy with docetaxel or oxaliplatin. Patients from an ongoing prospective study, who had received adjuvant chemotherapy with docetaxel or oxaliplatin in 2011-2012 were invited to participate. The patients underwent a thorough examination with interview, neurological examination, questionnaires, assessment tools, nerve conduction studies (NCS), quantitative sensory testing, MScan motor unit number estimation (MUNE), and corneal confocal microscopy (CCM). Patients were divided into no, possible, probable, and confirmed CIPN. Out of the 132 eligible patients, 63 agreed to participate: 28 had received docetaxel and 35 had received oxaliplatin. Forty-one percent had confirmed CIPN, 34% possible or probable CIPN, and 22% did not have CIPN. The CIPN was characterized mainly by sensory nerve fiber loss, with a more pronounced large fiber than small fiber loss but also some motor fiber loss identified on NCS and MUNE. In general, patients had mild neuropathy with relatively low scores on assessment tools and no association with mood and quality of life. CCM was not useful as a diagnostic tool. Of the patients with probable or confirmed CIPN, 30% experienced pain, which was most often mild, but still interfered moderately with daily life in 20-25% and was associated with lower quality of life. CIPN was confirmed in 41% 5 years after chemotherapy. The neuropathy was generally mild, but in patients with neuropathic pain it was associated with lower quality of life. This article is protected by copyright. All rights reserved.
Learn More >Recent studies suggest that sensory phenotyping may provide critical information for the diagnosis and management of patients with chronic neuropathic pain (NP). However, many formal quantitative sensory testing (QST) paradigms require expensive equipment, a dedicated location, and substantial time commitments on the part of patient and examiner, highlighting the need for a convenient and portable "bedside" QST battery. We developed and tested a bedside QST battery in a sample of patients with chronic NP.
Learn More >Pain is a major source of global suffering, with women bearing the greatest burden. Alongside biology, psychological and social factors, including gender, help explain these differences. However, there has been no direct attempt to develop a unified social psychological model of men and women's pain. By drawing on approaches to both gender and pain, a gender context model of pain is presented. It proposes that pain is partly influenced by the gender context in which it occurs, which operates at both individual and interpersonal levels. The model is used to structure an appraisal of the existing evidence around gender and pain, and explore whether the model helps explain why such variation occurs. It is argued that despite evidence for an association between gender and pain, there are empirical gaps that need to be addressed. Implications and directions for future investigations into sex, gender and pain are considered.
Learn More >Neuropathic pain (NP) is common in patients presenting with low back related leg pain. Accurate diagnosis of NP is fundamental to ensure appropriate intervention. In the absence of a clear gold standard, expert opinion provides a useful methodology to progress research and clinical practice. The aim of this study was to achieve expert consensus on a list of clinical indicators to identify NP in low back related leg pain.
Learn More >Mechanisms resulting in abdominal pain include altered neuro-immune interactions in the gastrointestinal tract, but the signaling processes that link immune activation with visceral hypersensitivity are unresolved. We hypothesized that enteric glia link the neural and immune systems of the gut and that communication between enteric glia and immune cells modulates the development of visceral hypersensitivity. To this end, we manipulated a major mechanism of glial intercellular communication that requires connexin-43 and assessed the effects on acute and chronic inflammation, visceral hypersensitivity, and immune responses. Deleting connexin-43 in glia protected against the development of visceral hypersensitivity following chronic colitis. Mechanistically, the protective effects of glial manipulation were mediated by disrupting the glial-mediated activation of macrophages through the macrophage colony-stimulating factor. Collectively, our data identified enteric glia as a critical link between gastrointestinal neural and immune systems that could be harnessed by therapies to ameliorate abdominal pain.
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