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The peripheral nervous system (PNS) connects the central nervous system (CNS) with the rest of the body to regulate many physiological functions and is therapeutically targeted to treat diseases such as epilepsy, depression, intestinal dysmotility, chronic pain, and more. However, we still lack understanding of PNS innervation in most organs because the large span, diffuse nature, and small terminal nerve bundle fibers have precluded whole-organism, high resolution mapping of the PNS. We sought to produce a comprehensive peripheral nerve atlas for use in future interrogation of neural circuitry and selection of targets for neuromodulation.
Learn More >Pain is one of the most common health problems and has a severe impact on quality of life. Yet, a suitable and efficient treatment is still not available for all patient populations suffering from pain. Interestingly, recent research shows that low threshold mechanosensory C-tactile (CT) fibres have a modulatory influence on pain. CT-fibres are activated by slow gentle stroking of the hairy skin, providing a pleasant sensation. Consequently, slow gentle stroking is known as affective touch. Currently, a clear overview of the way affective touch modulates pain, at a neural level, is missing. This review aims to present such an overview. To explain the interaction between affective touch and pain, first the neural basis of the affective touch system and the neural processing of pain will be described. To clarify these systems, a schematic illustration will be provided in every section. Hereafter, a novel model of interactions between affective touch and pain systems will be introduced. Finally, since affective touch might be suitable as a new treatment for chronic pain, possible clinical implications will be discussed.
Learn More >This special issue is a tribute to our mentor, colleague and friend, Gavril W. Pasternak, MD, PhD. Homage to the breadth and depth of his work (~ 450 publications) over a 40 career in pharmacology and medicine cannot be captured fully in one special issue, but the 22 papers collected herein represent seven of the topics near and dear to Gav's heart, and the colleagues, friends and mentees who held him near to theirs. The seven themes include: (1) sites and mechanisms of opioid actions in vivo; (2) development of novel analgesic agents; (3) opioid tolerance, withdrawal and addiction: mechanisms and treatment; (4) opioid receptor splice variants; (5) novel research tools and approaches; (6) receptor signaling and crosstalk in vitro; and (7) mentorship. This introduction to the issue summarizes contributions and includes formal and personal remembrances of Gav that illustrate his personality, warmth, and dedication to making a difference in patient care and people's lives.
Learn More >Increasing dietary intake of n-3 EPA+DHA and lowering dietary n-6 LA is under investigation as a therapeutic diet for improving chronic pain syndromes as well as other health outcomes. Herein we describe the diet methodology used to modulate intake of n-3 and n-6 PUFA in a free living migraine headache population and report on nutrient intake, BMI and diet acceptability achieved at week 16 of the intensive diet intervention and week 22 follow-up time-point.
Learn More >Afferents from the C2 spinal nerve (SN) and trigeminal nerve (TN) innervate neighboring cranial territories and their convergence on the upper cervical dorsal horn neurons represents neural substrate of pain referral in primary headache disorders. Unfortunately, little is known about trigeminocervical input to the major spinal nociceptive-projection area lamina I. Here we used ex-vivo brainstem-cervical cord preparation for the visually-guided whole-cell recording from the upper cervical lamina I neurons. We show that 50% of them receive convergent monosynaptic input from both nerves, whereas 35% and 11% of neurons receive specific supply from the C2 SN and TN, respectively. Altogether, ten distinct patterns of synaptic input from the C2 SN and TN to lamina I neurons could be identified. Although stimulation of both nerves evoked excitatory/inhibitory responses, more numerous pure inhibitory inputs arose from the TN. We show that cervical and trigeminal nociceptors converge on to lamina I projection and inhibitory neurons. Thus, trigeminocervical input in lamina I is processed in both nerve-specific and convergent circuitries. Afferent convergence on to inhibitory interneurons serves as a feedforward mechanism balancing excitatory drive to projection neurons. Disruption of this balance may cause pain in primary headache syndromes.
Learn More >Deprescribing is the systematic process of discontinuing drugs when harms outweigh the benefits. We conducted semi-structured telephone interviews with twenty-two general practitioners (GPs) who had prescribed or deprescribed opioids in patients with chronic non-cancer pain within the last six months to investigate the barriers and facilitators to deprescribing opioid analgesics in patients with chronic non-cancer pain. We also explored GPs' perspectives on the available resources to assist them with opioid deprescribing. Interviews were audio-recorded, transcribed verbatim and then coded using an iterative process until data saturation reached. The thematic analysis process identified themes, first as concepts, then refined to overarching themes after the merging of similar subthemes.Themes exploring barriers to deprescribing highlighted the difficulties GPs face while considering patient factors and varying prescribing practices within the confines of the health system. Patient motivation and doctor-patient rapport were central factors to facilitate deprescribing and GPs considered the most important deprescribing resource to be a multidisciplinary network of clinicians to support themselves and their patients. Therefore, although GPs emphasised the importance of deprescribing opioid analgesics, they also expressed many barriers relating to managing complex pain conditions, patient factors and varying prescribing practices between clinicians. Some of these barriers could be mitigated by GPs having time and resources to educate and build rapport with their patients. This suggests the need for further development of multimodal resources and improved support through the public health system to enable GPs to prioritise patient-centred care.
Learn More >The present study examined the role of attention control in understanding the development of negatively-biased pain memories as well as its moderating role in the relationship between pain catastrophizing and negatively-biased pain memories. Youth with chronic pain (N = 105) performed a cold pressor task (CPT) and completed self-report measures of state/trait pain catastrophizing and attention control, with the latter comprising both attention focusing and attention shifting. Two weeks after the CPT, youth's pain-related memories were elicited via telephone allowing to compute pain and anxiety memory bias indices (i.e., recalling pain intensity or pain-related anxiety, respectively, as higher than initially reported). Results indicated no main effects of attention control and pain catastrophizing on pain memories. However, both components of attention control (i.e., attention focusing and attention shifting) moderated the impact of pain catastrophizing on youth's memory bias, with opposite interaction effects. Specifically, whereas high levels of attention shifting buffered the influence of high pain catastrophizing on the development of pain memory bias, high levels of attention focusing strengthened the influence of high pain catastrophizing on the development of anxiety memory bias. Interaction effects were confined to trait catastrophizing (i.e., not state catastrophizing). Theoretical and clinical implications are discussed. PERSPECTIVE: This article investigates the role of attention control in the development of negatively-biased pain memories in children with chronic pain. Findings underscore the importance of targeting differential components of attention control and can inform intervention efforts to minimize the development of negatively biased pain memories in youth with chronic pain.
Learn More >This study compared perceptions of the burden of patient care and associated clinical judgments between physicians and people with chronic pain (PWCP) in a 2 × 3 × 2 between-subjects design that varied participant type, patient-reported pain severity (4-6-8/10), and supporting medical evidence (low/high). 109 physicians and 476 American Chronic Pain Association members were randomly assigned to one of six conditions. Respondents estimated the clinical burden they would assume as the treating physician of a hypothetical patient with chronic low back pain, and made clinical judgments regarding that patient. Physician burden ratings were significantly higher than PWCP ratings, and clinical impressions (e.g., trust in pain report, medical attribution) and management concerns (e.g., opioid abuse risk) were relatively less favorable. Neither pain severity nor medical evidence affected burden ratings significantly. High medical evidence was associated with more favorable clinical impressions; higher pain severity led to more discounting of patient pain reports. Burden was significantly correlated with a range of clinical judgments. Results indicate that physicians and people with chronic pain differ in their perceptions of provider burden and related clinical judgments in ways that could impact treatment collaboration. Further research is needed that examines provider burden in actual clinical practice. Perspective Physicians and people with chronic pain (PWCP) estimated the clinical burden of patient care and made judgments about a hypothetical patient with chronic pain. Physician burden ratings were higher and clinical judgments less favorable, relative to PWCP respondents. These differences could impact treatment collaboration and merit study in clinical practice.
Learn More >Persistent low back and pelvic pain (LBPP) is a postpartum-specific health problem. Sleep disturbances' association with persistent LBPP is not yet clear. We aimed to examine the cross-sectional association between sleep disturbance and persistent LBPP at 4 months postpartum.
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