Pain

Reliable and objective biomarkers promise to improve the assessment and treatment of chronic pain. Resting-state electroencephalography (EEG) is broadly available, easy-to-use, cost-efficient and, therefore, appealing as a potential biomarker of chronic pain. However, results of EEG studies are heterogeneous. We therefore conducted a systematic review (PROSPERO CRD42021272622) of quantitative resting state EEG and magnetoencephalography (MEG) studies in adult patients suffering from different types of chronic pain...

Chronic pain involves sensitization of nociceptors and synaptic transmission of painful signals in nociceptive circuits in the dorsal horn of the spinal cord. We investigated the contribution of clathrin-dependent endocytosis to sensitization of nociceptors by G protein-coupled receptors (GPCRs) and to synaptic transmission in spinal nociceptive circuits. We determined whether therapeutic targeting of endocytosis could ameliorate pain. mRNA encoding dynamin (Dnm) 1-3 and adaptor-associated protein kinase 1 (AAK1), which mediate clathrin-dependent endocytosis, were localized to primary sensory neurons of dorsal root ganglia of mouse and human and to spinal neurons in the dorsal horn of the mouse spinal cord by RNAScope®...

Specialized pro-resolving mediators (SPMs) have demonstrated potent analgesic actions in animal models of pathological pain. The actions of SPMs in acute and chronic itch are currently unknown. Recently, n-3 docosapentaenoic acid (DPA) was found to be a substrate for the biosynthesis of several novel families of SPMs; 3-oxa-PD1n-3 DPA (3-oxa-PD1) is an oxidation-resistant metabolic stable analogue of the n-3 DPA-derived protectin D1 (PD1). Herein, we demonstrate that 3-oxa-PD1 effectively reduces both acute and chronic itch in mouse models...

Mild traumatic brain injury, mTBI, is a leading cause of disability worldwide, with acute pain manifesting as one of its most debilitating symptoms. Understanding acute post-injury pain is important since it is a strong predictor of long-term outcomes. In this study, we imaged the brains of 157 patients with mTBI, following a motorized vehicle collision. We extracted white matter structural connectivity networks and used a machine learning approach to predict acute pain. Stronger white matter tracts within the sensorimotor, thalamic-cortical, and default-mode systems predicted 20% of the variance in pain severity within 72 hours of the injury...

There are concerns that cannabis use disorder (CUD) may develop in chronic pain patients prescribed medical cannabis (MC). The criteria for CUD according to the Statistical Manual for Mental Disorders Version 5 (DSM-5) were not developed for identification of patients using cannabis for therapeutic reasons. In addition, some items of CUD might be attributed to the desire of the patient to relieve the pain. Therefore, alternative strategies are needed to identify the true prevalence of CUD in persons with chronic pain being treated with MC...

Sleep loss heightens pain sensitivity, but the pathways underlying this association are not known. Given that experimental sleep disruption induces increases in cellular inflammation as well as selective loss of slow wave, N3 sleep, this study examined whether these mechanisms contribute to pain sensitivity following sleep loss in healthy adults. This assessor-blinded, cross-over sleep condition, single-site, randomized clinical trial enrolled 95 healthy adults (mean [SD] age, 27.8 [6.4]; female, 44 [53.7%])...

The bladder wall is innervated by a complex network of afferent nerves that detect bladder stretch during filling. Sensory signals, generated in response to distension, are relayed to the spinal cord and brain to evoke physiological and painful sensations and regulate urine storage and voiding. Hyperexcitability of these sensory pathways is a key component in the development of chronic bladder hypersensitivity disorders including interstitial cystitis/bladder pain syndrome and overactive bladder syndrome. Despite this, the full array of ion channels that regulate bladder afferent responses to mechanical stimuli have yet to be determined...

Recovery from surgery is quicker in the postpartum period, and this may reflect oxytocin action in the spinal cord. We hypothesized that intrathecal injection of oxytocin would speed recovery from pain and disability after major surgery. Ninety-eight individuals undergoing elective total hip arthroplasty were randomized to receive either intrathecal oxytocin (100 μg) or saline. Participants completed diaries assessing pain and opioid use daily and disability weekly, and they wore an accelerometer beginning 2 weeks before surgery until 8 weeks after...

The increased presence of senescent cells in different neurological diseases suggests the contribution of senescence in the pathophysiology of neurodegenerative disorders. Microglia can adapt to any type of disturbance of the homeostasis of the central nervous system, and its altered activity can lead to permanent and unresolvable damage. The aim of this work was to characterize the behavioural phenotype of spared nerve injury mice and then associate it with senescence-related mechanisms. In this work, we investigated the timing of the onset of anxiety, depression, or memory decline associated with peripheral neuropathic pain and their correlation with the presence of microglial cellular senescence...

Descending control of nociception (DCN; also known as conditioned pain modulation [CPM], the behavioral correlate of diffuse noxious inhibitory controls) is the phenomenon whereby pain inhibits pain in another part of the body and is the subject of increasing study because it may represent a biomarker of chronic pain. We recently discovered that pain modulation on the application of a DCN paradigm involving low-intensity test stimuli occurs in the direction of hyperalgesia in healthy mice and rats, whereas the use of high-intensity stimuli produces analgesia...

Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a common and debilitating disease with poor treatment outcomes. Studies from the Multidisciplinary Approach to the study of chronic Pelvic Pain (MAPP) research network established that IC/BPS patients with chronic overlapping pain conditions (COPCs) experience poorer quality of life and more severe symptoms, yet the neurobiological correlates of this subtype are largely unknown. We previously showed that ex-vivo Toll-Like Receptor 4 (TLR4) cytokine/chemokine release is associated with the presence of COPCs, as well as widespread pain and experimental pain sensitivity women with IC/BPS...

The nucleus of the solitary tract (NTS) contains pro-opiomelanocortin (POMC) neurons that are 1 of the 2 major sources of β-endorphin in the brain. The functional role of these NTSPOMC neurons in nociceptive and cardiorespiratory function is debated. We have shown that NTSPOMC optogenetic activation produces bradycardia and transient apnoea in a working heart-brainstem preparation and chemogenetic activation with an engineered ion channel (PSAM) produced opioidergic analgesia in vivo. To better define the role of the NTSPOMC neurons in behaving animals, we adopted in vivo optogenetics (ChrimsonR) and excitatory/inhibitory chemogenetic DREADD (hM3Dq/hM4Di) strategies in POMC-Cre mice...

The increasing demand for pain management and limited resources available highlight the need to measure treatment effectiveness. We analysed data collected at 75 specialist persistent pain services located in Australia and New Zealand to calculate the overall treatment outcome for patients receiving care during 2014 to 2020. Sociodemographic and clinical information was provided for 23,915 patients, along with patient-reported measures assessing pain, pain interference, depression, anxiety, stress, pain catastrophizing, and pain self-efficacy...

Functional changes in motor planning-related brain regions might indicate that feedback-enhanced functional motor training may be effective for CRPS rehabilitation.

Migraine is a common disabling disease with a complex pathophysiology. Headache is a frequent side effect after intravenous adenosine administration, while adenosine receptor antagonist, caffeine, relieves migraine headache. These observations suggest a possible involvement of adenosine signaling in headache and migraine pathophysiology.In a randomized, double-blinded, placebo-controlled, crossover study, 18 participants diagnosed with migraine without aura received 120 µg/kg/min adenosine or placebo over 20 minutes...

Referred sensations (RS) are a common clinical phenomenon in patients with musculoskeletal pain, however the underlying mechanisms of RS and implications for diagnosis and management are poorly understood. The location of referral seems to have a preferred site but studies have suggested it can be redirected to a site of previous injury and pain. However, it is not known if the same phenomenon can occur for a much shorter-lasting painful stimulus in the trigeminal system. The aim of this study was to assess if RS location elicited with standardized palpation of the masseter muscle could be altered following a 10-minute painful infusion of hypertonic saline into the retromolar region...

Temporomandibular disorders (TMD) include a group of musculoskeletal disorders that may involve increased responsiveness of nociceptive neurons in the central nervous system (i.e. central sensitization). To test this hypothesis further, the present study examined whether, as compared with healthy subjects, patients with chronic TMD have a greater susceptibility to develop secondary mechanical hyperalgesia - a phenomenon that can be confidently attributed to central sensitization.In this case-control study, we assessed the area of secondary mechanical hyperalgesia induced experimentally by delivering high-frequency electrical stimulation (HFS) to the volar forearm skin in 20 participants with chronic TMD and 20 matched healthy controls...

Pain is a common symptom in patients referred to polyneuropathy assessment. Diagnostic evaluation and choice of treatment may depend on whether the pain is likely to be neuropathic or not. The present study aimed to investigate the diagnostic accuracy of three tools commonly used to differentiate between neuropathic and non-neuropathic pain. To accomplish this, we included patients with bilateral distal lower extremity pain, referred to neurological outpatient clinics at five Norwegian University hospitals for polyneuropathy assessment...

To enhance patient-centred care of people with hip pain, we need a comprehensive understanding of peoples' beliefs about their hip pain. This systematic review explored middle-aged and older adults' beliefs and expectations about chronic hip pain and its care across different healthcare settings and contexts. This review was a synthesis of qualitative studies using a framework synthesis approach. We searched five databases: MEDLINE, CINAHL, The Cochrane Central Register of Controlled Trials, EMBASE, and PsycINFO...

The objective of this systematic review is to quantify the association between recovery expectations and return-to-work outcomes in adults with musculoskeletal pain conditions. In addition, this review has the second objective to compare the predictive utility of single-item and multi-item recovery expectation scales on return-to-work outcomes. Relevant articles were selected from Embase, PsycINFO, PubMed, Cochrane and manual searches. Studies that assessed recovery expectations as predictors of return-to-work outcomes in adults with musculoskeletal pain conditions were eligible...