Pain
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The analgesic effects of morphine are mediated, in part, by periaqueductal gray (PAG) neurons that project to the rostral ventromedial medulla (RVM). Although much of the neural circuitry within the RVM has been described, the relationship between RVM neurons and PAG input and spinal output is not known. The objective of this study was to determine whether GABAergic output neurons from the PAG target RVM reticulospinal neurons. ⋯ Similar to the pattern reported above, both GAD67- and non-GAD67-immunoreactive PAG neurons project to RVM ON, OFF, and Neutral cells in the RVM. These inputs include a GAD67-immunoreactive projection to a GAD67-immunoreactive ON cell and non-GAD67 projections to GAD67-immunoreactive OFF cells. This pattern is consistent with PAG neurons producing antinociception by direct excitation of RVM OFF cells and inhibition of ON cells.
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We are studying an endogenous, oxytocinergic analgesia system to obtain more information about normal and pathological pain processes. In the recent years, this oxytocinergic system has been shown to be involved in normal and pathological pain suppression. The paraventricular nucleus (PVN) of the hypothalamus is an important source of brain oxytocin (OT). ⋯ Sciatic loose ligature was used as the experimental method to produce neuropathic pain. The main findings were (1) Chronic pain experiments in animals showed that the stimulation of the anterior part of the PVN increased OT concentration and produced analgesia states, as measured by von Frey, cold, and heat plantar tests. (2) Differential effects were produced by electrical stimulation of the anterior or posterior regions of the PVN; electrical stimulation of the anterior part of the PVN enhanced the OT concentration in CSF and plasma, and it also increased OT protein concentrations in the spinal cord tissue; in contrast, the stimulation of the posterior part of the PVN only increased OT concentrations in CSF. These results suggest the participation of an endogenous analgesia system mediated by OT.
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The roles of ion channels in sensory neurons were examined in experimental models of muscle pain in the rat. Rats were injected with 50 microl of 4% carrageenan or subjected to an eccentric exercise (ECC) of the gastrocnemius muscle (GM). The Randall-Selitto and von Frey tests were performed on the calves to evaluate mechanical hyperalgesia of the muscle. ⋯ Antagonists to TRP channels and ASICs showed suppressive effects for both carrageenan- and ECC-induced muscle hyperalgesia. The carrageenan injection and ECC models are useful models of acute inflammatory pain and delayed onset muscle soreness (DOMS), respectively, and the time course and underlying etiology might be different. TRP channels and ASICs are closely related to the development of muscle mechanical hyperalgesia, and TRPV1 is involved in ECC-induced DOMS.
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Randomized Controlled Trial
Acidic buffer induced muscle pain evokes referred pain and mechanical hyperalgesia in humans.
While tissue acidosis causes local deep-tissue pain, its effect on referred pain and mechanical muscle hyperalgesia is unknown. The aim of this study was to investigate a human experimental acidic muscle pain model using a randomized, controlled, single-blinded study design. Seventy-two subjects (36 female) participated in three visits, each involving one 15 min intramuscular infusion into the anterior tibialis muscle: acidic phosphate buffer (pH 5.2) at 40 ml/h (N=69) or 20 ml/h (N=54), normal phosphate buffer (pH 7.3) at 40 ml/h (N=70), or isotonic saline at 40 ml/h (N=19). ⋯ PPTs decreased at the ankle in those with referred pain in response to acidic buffer, i.e. referred mechanical hyperalgesia, but not at the foot. No pain or changes in PPTs occurred in the contralateral leg. These results demonstrate muscle acidosis can lead to local and referred pain and hyperalgesia, with significant sex differences in development of referred pain.
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Although patients with a depressive disorder report often of pain, their sensitivity to experimental pain is controversial, probably due to differences in sensory testing methods and to the lack of normal values. Therefore, we used a standardized and validated comprehensive sensory testing paradigm to assess the peripheral and central nervous system performance in depressive patients compared to healthy controls and chronic pain patients with fibromyalgia syndrome (FMS), in which depression is a common comorbidity. Twenty-five depressive psychiatric inpatients (pain-free: n=20), 35 FMS outpatients and 25 healthy controls underwent quantitative sensory testing (QST), including thermal and mechanical detection and pain thresholds, pain sensitivity and responsiveness to repetitive noxious mechanical stimuli (wind-up). ⋯ In the mostly pain-free patients signs of an enhanced central hyperexcitability are even more pronounced than usually found in chronic pain patients (e.g. FMS), indicating common mechanisms in depressive disorder and chronic pain in accordance with the assumption of non-pain associated mechanisms in depressive disorder for central hyperexcitability, e.g. by inhibited serotonergic function. Furthermore, this trial demonstrates the feasibility of QST in depressive patients.