Articles: hyperalgesia.
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The authors previously reported that noncoding microRNA miR-219-5p is down-regulated in the spinal cord in a nociceptive state. The ventral tegmental area also plays critical roles in modulating nociception, although the underlying mechanism remains unknown. The authors hypothesized that miR-219-5p in the ventral tegmental area also may modulate nociception. ⋯ Down-regulation of astroglial miR-219-5p in ventral tegmental area induced nociceptive responses are mediated by astroglial coiled-coil and C2 domain containing 1A/nuclear factor-κB signaling and elevated dopamine neuron activity.
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The effectiveness of Botulinum-neurotoxin A (BoNT/A) to treat pain in human pain models is very divergent. This study was conducted to clarify if the pain models or the route of BoNT/A application might be responsible for these divergent findings. ⋯ The study demonstrates that BoNT/A (Incobotulinumtoxin A) has differential effects in human pain models: It reduces the neurogenic flare and had a moderate analgesic effects in low frequency but not high frequency current stimulation of cutaneous afferent fibers at C-fiber strength; BoNT/A had no effect in capsaicin-induced (CAPS) neurogenic flare or pain, or on hyperalgesia to mechanical or heat stimuli in both pain models. Intracutaneous BoNT/A increases warm and heat pain thresholds on naïve skin.
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Randomized Controlled Trial
Role of capsaicin- and heat-sensitive afferents in stimulation of acupoint induced pain and analgesia in humans.
We investigated role of capsaicin-sensitive afferents within and without the areas of Zusanli (ST36)/Shangjuxu (ST37) acupoints along the stomach (ST) meridian in the perception and modulation of pain assessed by visual analog scale of pain and its distribution rated by subjects, pressure pain threshold (PPT), and heat pain threshold (HPT) in humans. Compared with the treatment of non-acupoint area, capsaicin (100µg/50µl) administered into either ST36 or ST37 acupoint caused the strongest pain intensity and the most extensive pain distribution, followed by rapid onset, bilateral, long-lasting secondary mechanical hyperalgesia and slower onset secondary heat hypoalgesia (1day after the capsaicin treatment). ⋯ Upon trapezius muscle pain elicited by the i.m. injection of 5.8% saline, pre-emptive treatment of the contralateral ST36 acupoint with 43°C heating-needle stimulation alleviated the ongoing muscle pain, reduced painful area, and reversed the decrease in HPT. It is suggested that (1) pain elicited from the acupoint and non-acupoint areas differs significantly, which are supposed to be dependent on the different distributions and contributions of capsaicin-sensitive afferents. (2) Non-painful heat stimulation is a valid approach in prevention of ongoing muscle pain with associated post-effects of peripheral and central sensitization.
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Peripheral tissue inflammation or injury causes glutamate release from nociceptive axons, keratinocytes, and Schwann cells, resulting in thermal hypersensitivity. However, the detailed molecular mechanisms underlying glutamate-induced thermal hypersensitivity are unknown. The aim of this study was to clarify the involvement of peripheral transient receptor potential (TRP) TRP vanilloid 1 (TRPV1), TRP ankyrin 1 (TRPA1), and protein kinase C epsilon (PKCε) in glutamate-induced pain hypersensitivity. ⋯ PKCε phosphorylation in TG was significantly enhanced following glutamate injection into the facial skin. Moreover, neuronal activity of TG neurons was significantly increased following facial glutamate treatment. The present findings suggest that sensitization of TRPA1 and/or TRPV1 through mGluR5 signaling via PKCε is involved in facial thermal and mechanical hypersensitivity.
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Regular physical activity prevents the development of chronic muscle pain through the modulation of central mechanisms that involve rostral ventromedial medulla (RVM). We tested if pharmacological blockade or genetic deletion of mu-opioid receptors in physically active mice modulates excitatory and inhibitory systems in the RVM in an activity-induced hyperalgesia model. We examined response frequency to mechanical stimulation of the paw, muscle withdrawal thresholds, and expression of phosphorylation of the NR1 subunit of the N-methyl-D-aspartate receptor (p-NR1) and serotonin transporter (SERT) in the RVM. ⋯ Physically active, naloxone-treated, and MOR mice showed significant increases in SERT immunoreactivity when compared with wild-type physically active control mice. Blockade of SERT in the RVM in sedentary mice reversed the activity-induced hyperalgesia of the paw and muscle. These results suggest that analgesia induced by 5 days of wheel running is mediated by mu-opioid receptors through the modulation of SERT, but not p-NR1, in RVM.