Pain
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It has been proposed that complex regional pain syndrome (CRPS) is a post-traumatic autoimmune disease. Previously, we observed that B cells are required for the full expression of CRPS-like changes in a mouse tibia fracture model and that serum immunoglobulin M (IgM) antibodies from fracture mice have pronociceptive effects in muMT fracture mice lacking B cells. The current study evaluated the pronociceptive effects of injecting CRPS patient serum or antibodies into muMT fracture mice by measuring hind paw allodynia and unweighting changes. ⋯ Early (1-12 months after injury) CRPS patient (n = 20) sera were always pronociceptive after systemic injection, and chronic (>12 months after injury) CRPS sera were rarely pronociceptive (2/20 patients), while sera from normal subjects (n = 20) and from patients with uncomplicated recoveries from orthopedic surgery and/or fracture (n = 15) were never pronociceptive. Increased CRPS serum IgM binding was observed for keratin 16, histone 3.2, gamma actin, and alpha enolase autoantigens. We postulate that CRPS patient IgM antibodies bind to neoantigens in the fracture mouse skin and spinal cord to initiate a regionally restricted pronociceptive complement response potentially contributing to the CRPS disease process.
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International clinical practice guidelines for low back pain (LBP) contain consistent recommendations including universal provision of information and advice to remain active, discouraging routine referral for imaging, and limited prescription of opioids. This systematic review describes usual care provided by first-contact physicians to patients with LBP. Studies that reported the assessments and care provided to people with LBP in family practice and emergency departments (EDs) from January 2000 to May 2019 were identified by searches of PubMed, EMBASE, and CINAHL. ⋯ Large numbers of patients who saw a physician for LBP received care that is inconsistent with evidence-based clinical practice guidelines. Usual care included overuse of imaging and opioid prescription and underuse of advice and information. Suboptimal care may contribute to the massive burden of the condition worldwide.
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Chronic pain is known to alter the brain's network dynamics. These dynamics are often demonstrated by identifying alterations in the brain network topology. A common approach used for this purpose is graph theory. ⋯ These regions have been identified as brain hubs (ie, regions that are responsible for orchestrating communication between other brain regions) and are therefore known to be more vulnerable in brain disorders including chronic pain. We were furthermore able to uncover associations between these altered brain network properties and the symptoms reported by patients. Our findings indicate that chronic neck pain patients reflect brain network alterations and that targeting the brain in patients might be of utmost importance.
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This study aims to investigate whether intranetwork dynamic functional connectivity and causal interactions of the salience network is altered in the interictal term of migraine. Thirty-two healthy controls, 37 migraineurs without aura, and 20 migraineurs with aura were recruited. Participants underwent a T1-weighted scan and resting-state fMRI protocol inside a 1.5T MR scanner. ⋯ Variance of dynamic conditional correlation was higher in migraine with aura vs healthy controls and migraine with aura vs without aura between the right insula and dorsal anterior cingulate cortex (P < 0.011, P < 0.026), and in migraine with aura vs healthy controls between the dorsal anterior cingulate and left prefrontal cortex (P < 0.021). Causality was weaker in the <0.05 Hz frequency range between the salience and dorsal attention networks in migraine with aura (P < 0.032). Overall, migraineurs with aura exhibit more fluctuating connections in the salience network, which also affect network interactions, and could be connected to altered cortical excitability and increased sensory gain.
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Several reports support the idea that µ- and δ-opioid receptors (ORs) may exist as heterodimers in brain regions involved in pain signaling. The unique pharmacology of these heteromers may present a novel analgesic target. However, the role of µ-δ heteromers in sensory neurons involved in pain and opioid analgesia remains unclear, particularly during neuropathic pain. ⋯ Electrophysiologic studies showed that CYM51010 inhibited the C-component and windup phenomenon in spinal wide dynamic range neurons of SNL rats. The pain inhibitory effects of CYM51010 persisted in morphine-tolerant rats but was markedly attenuated in µ-OR knockout mice. Our studies show that spinal nerve injury may increase µ-δ heterodimerization in uninjured DRG neurons, and that µ-δ heteromers may be a potential therapeutic target for relieving neuropathic pain, even under conditions of morphine tolerance.