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Neuropathic pain is believed to arise from damage to nociceptive C fibres in diabetic neuropathy (DN). We have utilised corneal confocal microscopy (CCM) to quantify the severity of small nerve fibre damage in relation to the severity of neuropathic pain and quality of life (QoL) in patients with and without painful DN. 30 controls and patients with painful (n = 78) and painless (n = 62) DN underwent assessment of large and small nerve fibre function, CCM, neuropathic symptoms (small fibre neuropathy symptom inventory questionnaire, neuropathic pain scale) and QoL (SF-36, pre-R-ODS and hospital anxiety and depression scale). Patients with painful compared to painless DN, had comparable neurophysiology and vibration perception, but lower corneal nerve fibre density (20.1 ± 0.87 vs. 24.13 ± 0.91, P = 0.005), branch density (44.4 ± 3.31 vs. 57.74 ± 3.98, P = 0.03), length (19.61 ± 0.81 vs. 22.77 ± 0.83, P = 0.01), inferior whorl length (18.03 ± 1.46 vs. 25.1 ± 1.95, P = 0.005) and cold sensation threshold (21.35 ± 0.99 vs. 26.08 ± 0.5, P < 0.0001) and higher warm sensation threshold (43.7 ± 0.49 vs. 41.37 ± 0.51, P = 0.004) indicative of small fibre damage. There was a significant association between all CCM parameters and the severity of painful neuropathic symptoms, depression score and QoL. CCM identifies small nerve fibre loss, which correlates with the severity of neuropathic symptoms and reduced QoL in patients with painful diabetic neuropathy.
Learn More >Medication overuse headache may be associated with widespread alterations along the thalamocortical pathway, a pathway involved in pain perception and disease progression. This study addressed whether brain metabolites in key regions of the thalamocortical pathway differed between chronic migraine patients with medication overuse headache and without medication overuse headache.
Learn More >Marijuana is increasingly utilized for the treatment of multiple medical problems, including back pain, in the United States. Although there is strong preclinical evidence supporting the promise of cannabinoids in the treatment of back pain, there is a paucity of clinical data supporting their use in clinical practice. Opioids are an important medication for the treatment of acute and chronic back pain, but utilization of opioid-based regimens have likely contributed to the growing opioid epidemic. The significant risk of morbidity, mortality, and dependence secondary to opioid medications have increased the interest in nonopioid medications, including cannabinoid-based pain regimens, in treating back pain. This review will provide an overview on the pharmacology, drug delivery methods, clinical evidence, and safety considerations critical to understanding the potential role of cannabinoids in the treatment of back pain.
Learn More >Healthy women have generally been found to have increased experimental pain perception and chronic pain has a higher prevalence in female as compared to male patients. However, no study has investigated whether pain intensity and pain perception thresholds are distinct or similar between sexes within various chronic pain entities. We investigated whether average pain intensities and pain thresholds assessed using quantitative sensory testing (QST) differed between women and men suffering from three distinct chronic pain conditions: Complex Regional Pain Syndrome (CRPS type I), peripheral nerve injury (PNI) or polyneuropathy (PNP), as compared to paired healthy volunteers.
Learn More >The primary objective of the proposed systematic review is to determine if there is an association between internalizing disorders and symptoms (ie, subclinical symptoms) and migraine in children and adolescents.
Learn More >To assess differences in tactile spatial acuity and in sensory-motor control between patients with chronic nonspecific neck pain (CNSNP) with and without neuropathic features (NF), as well as asymptomatic.
Learn More >Although tolerance serves as a major limitation in the long-term clinical use of opioids in patients with chronic severe pain, mechanisms of opioid tolerance are poorly understood. In this study, a morphine tolerance model was established by subcutaneously injecting male rats with morphine (10 mg/kg) twice a day for 10 consecutive days. In addition, a subset of morphine-tolerant rats underwent testosterone replacement therapy. The levels of mu-opioid receptor (MOR) mRNA and protein in the trigeminal ganglia (TGs) of morphine-tolerant versus control rats and of morphine-tolerant rats with vs. without testosterone replacement therapy were measured. We found that testosterone levels were significantly lower in morphine-tolerant rats than in the controls (1.248 ± 0.231 ng/ml vs. 2.223 ± 0.153 ng/ ml, respectively; p = 0.008). Furthermore, chronic morphine exposure led to a downregulation in the levels of MOR mRNA to 79.3%, and of MOR protein to 68.9%. Testosterone replacement therapy restored MOR mRNA and protein levels specifically in rats who had developed a tolerance to morphine, thereby suggesting a potential role of testosterone in the opioid-receptor response to chronic morphine exposure. In summary, our study provides evidence for the involvement of testosterone in the proper regulation of the peripheral MOR system in rats following prolonged morphine exposure. We also suggest that analgesic therapeutic measures should take into account the testosterone levels of patients who have built up a tolerance to morphine.
Learn More >The mesopontine tegmental anesthesia area (MPTA) is a small brainstem nucleus that, when exposed to minute quantities of GABA receptor agonists, induces a state of general anesthesia. In addition to immobility and analgesia this state is accompanied by widespread suppression of neural activity in the cerebral cortex and high delta-band power in the electroencephalogram. Collectively, MPTA neurons are known to project to a variety of forebrain targets which are known to relay to the cortex in a highly distributed manner. Here we ask whether ascending projections of individual MPTA neurons collateralize to several of these cortical relay nuclei, or access only one. Using rats, contrasting retrograde tracers were microinjected pairwise on one side into three ascending relays: the basal forebrain, the zona incerta-lateral hypothalamus and the intralaminar thalamic nuclear group. In addition, in separate animals, each target was microinjected bilaterally. MPTA neurons were then identified as being single-or double-labeled, indicating projection to one target nucleus or collateralization to both. Results indicated that double-labeling was rare, occurring on average in only 1.3% of the neurons sampled. The overwhelming majority of individual MPTA neurons showed specific connectivity, contributing to only one of the major ascending pathways, either ipsilaterally or contralaterally, but not bilaterally. This architecture would permit particular functional aspects of anesthetic loss-of-consciousness to be driven by specific subpopulations of MPTA neurons.
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