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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of transcutaneous electrical stimulation and systemic injection of phentolamine, a non-specific alpha-adrenergic antagonist, on the behavioral signs of mechanical allodynia and cold hyperalgesia in rats with nerve injury were investigated. Mechanical allodynia and cold hyperalgesia were evaluated by measuring the paw withdrawal frequency (PWF) resulting from repetitive application of a von Frey hair and the paw lift duration (PLD) at a cold temperature, respectively. After a unilateral nerve injury, both PWF and PLD increased in the injured hind paw. Application of low-frequency, high-intensity transcutaneous electrical stimulation (LFHI-TES) to the injured hind paw depressed the injury-induced increased PWF, whereas it had no effect on the injury-induced increased PLD. Naloxone reversed the LFHI-TES produced depression of PWF. Intraperitoneal administration of phentolamine depressed the injury-induced increased PLD without affecting the injury-induced increased PWF. Our results suggest that LFHI-TES, which activates the endogenous opioid systems, produces an antinociceptive effect that appears to be related to whether or not the pain is mediated by sympathetic activity.
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PMID:Differential antinociceptive effect of transcutaneous electrical stimulation on pain behavior sensitive or insensitive to phentolamine in neuropathic rats. 1123 6

The actions of different cholinergic agonists and antagonists were investigated on nociceptive afferents using the rat skin-saphenous nerve preparation, in vitro. Nicotine was able to weakly excite C-nociceptors and to induce a mild sensitization to heat stimulation (in 77% of tested fibers) in a dose-dependent manner (10(-)6 to 10(-)5 m), but it caused no alteration in mechanical responsiveness tested with von Frey hairs. Muscarine did not induce a significant nociceptor excitation, but almost all fibers exhibited a marked desensitization to mechanical and heat stimuli in a dose-dependent manner (from 10(-)6 to 10(-)4 m). The muscarinic effects could be prevented by the general muscarinic antagonist scopolamine (10(-)5 m), by the M3 antagonist 1,1-dimethyl-4-diphenylacetoxypiperidium oxide (10(-)6 m) co-applied with the M2 antagonist gallamine (10(-)5 m), and by gallamine alone. As positive control we used the relatively M2-selective agonist arecaidine (10(-)6 to 10(-)5 m), obtaining a similar desensitizing effect as with muscarine. Finally, we performed an immunocytochemical study that demonstrated the presence of M2 but not M3 receptors in thin epidermal nerve fibers of the rat hairy skin. Altogether, these data demonstrate opposite effects of nicotinic and muscarinic receptor stimulation on cutaneous nociceptors. M2 receptor-mediated depression of nociceptive responsiveness may convey a therapeutic, i.e., analgesic or antinociceptive, potential.
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PMID:Excitatory nicotinic and desensitizing muscarinic (M2) effects on C-nociceptors in isolated rat skin. 1131 14

We recently described a novel endogenous mechanism of peripheral antinociception, possibly involving activation of muscarinic M2 acetylcholine receptors that are expressed on nociceptive nerve endings and decrease their sensitivity. In the present study, this mechanism was scrutinized in skin taken from mice with targeted deletions of the muscarinic M2 receptor gene and, for control purposes, of the M4 receptor gene. Two different approaches were taken. Electrophysiologically the effects of muscarine on nociceptive afferents were investigated using the mouse skin-saphenous nerve preparation, in vitro. Muscarine did not excite nociceptors in the wild-type littermates (WT) and M4 knock-out (M4 KO) mice, but almost all fibers exhibited marked desensitization to mechanical and heat stimuli. Surprisingly, in the M2 KO mice, muscarine was able to excite C-nociceptors and to induce a mild sensitization to heat but caused no alteration in mechanical responsiveness tested with von Frey hairs. In the second, neurochemical approach, the heat-induced cutaneous release of calcitonin gene-related peptide (CGRP) was investigated to gain comparative data on the neurosecretory (vasodilatory) functions of the primary afferent neurons. The substantial increase of CGRP release evoked by noxious heat (47 degrees C) was diminished under muscarine by >50% in the WT and M4 KO animals but remained unaltered in the M2 KO mice. Together, these data provide direct evidence that M2 receptors on cutaneous nerve endings mediate effective depression of nociceptive responsiveness. This observation should be of interest for the development of novel classes of analgesic agents.
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PMID:Muscarinic M2 receptors on peripheral nerve endings: a molecular target of antinociception. 1204 34

Pain after surgery results in significant morbidity, and systemic opioids often fail to provide adequate analgesia without marked sedation and respiratory depression. Intrathecal morphine provides better analgesia, but is limited by delayed respiratory depression. Intrathecal injection of the cyclooxygenase inhibitor, ketorolac, has recently entered clinical trials, and the current study examined the interaction between intrathecal morphine and ketorolac to treat postoperative pain. We also sought to compare these treatments on a commonly used assessment of withdrawal threshold and a new assessment of spontaneous behavior after surgery. Male Sprague Dawley rats and underwent hind paw incision or subcostal laparotomy surgery. Intrathecal morphine, ketorolac, or their combination were injected on the first postoperative day, with outcome measure being return to pre-surgery withdrawal threshold with von Frey filament testing of the paw after paw incision, or return to pre-surgery exploratory activity after laparotomy. Intrathecal morphine completely reversed the effects of surgery in both models, but intrathecal ketorolac only partially reversed them. Ketorolac enhanced the potency of morphine several fold in both models, and did so synergistically after paw incision. In all cases drug potency was greater for spontaneous than elicited responses. These data confirm that spinal opioid receptor and cyclooxygenase enzyme inhibition diminish elicited tactile hypersensitivity after surgery, and that they similarly return spontaneous behavior to normal. Differences in drug potency could reflect fundamental differences in outcome measures or in the surgical procedures themselves. These data support combination study of intrathecal morphine and ketorolac for postoperative pain.
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PMID:Intrathecal morphine and ketorolac analgesia after surgery: comparison of spontaneous and elicited responses in rats. 1566 47

Reduced side-effect liability of opioids may enhance the patient's quality of life and decrease the incidence of opioid-insensitive pain. Literature offers few comparative data between different opioids at equianalgesic doses. Therefore morphine, fentanyl, buprenorphine, codeine, hydrocodone and oxycodone were compared for analgesic properties and side-effect profiles in rats. Analgesic efficacy was analysed using a tail withdrawal test for acute thermal nociception, a formalin test for chemically induced inflammatory pain and a von Frey test for mechanical hypersensitivity. For side-effect profiling inhibition of gastrointestinal activity was evaluated in a charcoal and ricinus oil test, arterial PCO(2) was determined for measuring respiratory depression, the discriminative stimulus properties linked to the narcotic cue were assessed using a drug discrimination learning test, and motor coordination was tested through rotarod performance. ED(50)'s for the occurrence of side-effects were compared to ED(50)'s in behavioural pain tests. Fentanyl had a strong analgesic potency and, compared to other opioids, an acceptable side-effect profiling at analgesic ED(50)'s. Also consistent was the ceiling effect of buprenorphine implying an increased safety margin for side-effects, but a decreased analgesic efficacy. Differences between opioids as observed in this study can have important indications for their use in acute as well as in the onset of chronic treatments.
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PMID:A preclinical comparison between different opioids: antinociceptive versus adverse effects. 1568 Jan 84

There is an association between depression and chronic pain, and some antidepressants exert antinociceptive effects in humans and laboratory animals. We examined the effects of fluvoxamine, a selective serotonin reuptake inhibitor, on mechanical allodynia and its mechanism of action in the mouse chronic pain model, which was prepared by partially ligating the sciatic nerve. The antiallodynic effect was measured using the von Frey test. Fluvoxamine produced antiallodynic effects following both systemic and intrathecal administration. In 5-hydroxytryptamine (5-HT)-depleted mice, prepared by intracerebroventricular injection of 5,7-dihyroxytryptamine, the fluvoxamine-induced antiallodynic effect was significantly attenuated. The antiallodynic effects of systemic fluvoxamine were also reduced by both systemic and intrathecal administration of ketanserin, a 5-HT2A/2C receptor antagonist. In addition, fluvoxamine also induced antinociceptive effect in the acute paw pressure test, and this effect was antagonized by the 5-HT3 receptor antagonist granisetron. These results indicate that fluvoxamine exerts its antiallodynic effects on neuropathic pain via descending 5-HT fibers and spinal 5-HT2A or 5-HT2C receptors, and the antinociception on acute mechanical pain via 5-HT3 receptors.
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PMID:Fluvoxamine, a selective serotonin reuptake inhibitor, exerts its antiallodynic effects on neuropathic pain in mice via 5-HT2A/2C receptors. 1684 19

Temporomandibular disorders (TMD) are common pain problems in the population with uncertain pathophysiology and mechanisms. The aim of this experimental study was to: (1) Establish an experimental pain model using electrical stimuli to describe characteristics of nociception from the human temporomandibular joint (TMJ) and overlying skin. (2) Test the hypothesis that there would be sex-related differences in TMJ sensitivity. Forty-three healthy subjects (24 men and 19 women) participated. Using two unipolar needle electrodes into the skin (above the TMJ) in one session or into the TMJ in the other session, sensory detection threshold (SDT), pain detection threshold (PDT), and summation threshold (SumT) were measured, before and after repetitive electrical stimulation. Painful repetitive electrical stimulation was applied for 20 min with individually adjustment of the intensity of the stimuli to keep the pain rating around five on a 0-10 cm visual analogue scale (VAS). Sensitivity to tactile and pin-prick stimuli were assessed at 11 sites around the TMJ using two von Frey nylon filaments (5.16 and 84.96 g), as well as pressure pain threshold (PPT) and pressure pain tolerance (PPTOL) before the stimulation, after 20 min of stimulation and finally 15 min after the end of stimulation. Numerical rating scale (NRS) from 0 to 100 was used to rate the intensity of applied von Frey filaments. SDT, PDT, and SumT were higher in the TMJ than in the skin. These three measures increased after painful repetitive stimulation for 20 min (de-sensitization). In contrast to this effect, a hypersensitivity to pin-prick stimuli was detected around the TMJ area on the stimulated side after 20 min of electrical stimulation in the TMJ, but not in the skin. A bilateral hyposensitivity to tactile stimuli was detected after skin and TMJ stimulation. PPT and PPTOL did not show a significant change over time. Except for lower TMJ PPTOLs in women than men there were no significant sex-related differences in mechanical or electrical measures. The present findings indicate differences in the elicitation of hypersensitivity following repetitive electrical stimulation of skin and deep tissues. The mechanisms underlying these findings are not clear but differences in the induction of long-term potentiation and depression is a possibility. From a clinical point of view, the lack of sex differences in most of the used measures indicates that the higher prevalence of women than men amongst patients with persistent TMJ pain problems not entirely can be ascribed to a higher sensitivity of the TMJ. Further studies will examine the somatosensory sensitivity of patients with TMJ pain problems.
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PMID:Somatosensory function following painful repetitive electrical stimulation of the human temporomandibular joint and skin. 1714 45

Changes in glycinergic neurotransmission in the spinal cord dorsal horn are critically involved in the development of pathological pain. Since the concentration of glycine in the synaptic cleft is controlled by specialized proteins, the glycine transporters GlyT1 and GlyT2, manipulation of this system might have significant effects on nociception. In the present study, we investigated the effects of the spinally applied glycine transporter inhibitors ALX 5407 (GlyT1) and ALX 1393 (GlyT2) on nociceptive behavior in the chronic constriction injury model of neuropathic pain in male Wistar rats. After implementation of neuropathy, the animals were injected with three dosages of ALX 5407 and ALX 1393 (10, 50 and 100 microg) via an intrathecal catheter (n = 8 each). Subsequently, nociceptive behavior was evaluated regarding thermal hyperalgesia (Hargreaves method) and mechanical sensitization (von Frey filaments) over 240 min after application. Inhibition of GlyT1 by ALX 5407 had differential dose-dependent effects. While the highest and the lowest concentrations were antinociceptive, the medium dose evoked pronociceptive effects. The GlyT2 inhibitor ALX 1393 was only effective in the highest concentration at which it exerted significant antinociception. However, in the same dose, ALX 1393 caused remarkable side effects such as respiratory depression and motor deficits in three animals. Our findings indicate that inhibition of glycine transporters is capable of evoking significant effects on nociceptive behavior in neuropathic pain. Whether glycine transporter inhibitors have the capability to gain clinical relevance as analgesic compounds on the long run has to be elucidated in further investigations.
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PMID:Differential effects of spinally applied glycine transporter inhibitors on nociception in a rat model of neuropathic pain. 1879 97

Clinical observations suggest that depressed patients were less sensitive to experimental pain than healthy subjects. However, few animal studies are reported concerning the association of depression and pain. The purpose of this study was to investigate the effects of unpredictable chronic mild stress (UCMS) induced depression on the perceived intensity of painful stimulation in rats. We measured the thermal and mechanical paw withdrawal thresholds (PWT) of normal and spinal nerve ligated (SNL) rats using hot plate test and von Frey test, respectively. The results showed that rats exposed to UCMS exhibited significantly higher thermal and mechanical pain thresholds in comparison to the non-depressed controls. In particular, the PWT of the SNL group was restored to nearly normal level after three weeks of UCMS, and even comparable to that of the control group. These results strongly suggest that the depressed subjects have decreased sensitivity to externally applied noxious stimulation, which is consistent with our previous findings.
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PMID:Increased thermal and mechanical nociceptive thresholds in rats with depressive-like behaviors. 2063 42

Altered pain responding in depression is a widely recognized but poorly understood phenomenon. The present study investigated nociceptive responding to acute (thermal and mechanical) and persistent (inflammatory) noxious stimuli in two animal models of depression, the olfactory bulbectomized (OB) and the Wistar-Kyoto (WKY) rat. In addition, this study examined if altered nociceptive behaviour was associated with changes in monoamine levels in discrete brain regions. OB rats exhibited mechanical allodynia (von Frey test) but not thermal hyperalgesia (hot plate and tail-flick tests) when compared to sham-operated counterparts. Formalin-induced nociceptive behaviour was both heightened and prolonged in OB versus sham-operated controls. An inverse correlation was observed between 5-hydroxyindoleacetic acid (5-HIAA) concentration in the hippocampus and amygdaloid cortex and nociceptive behaviour in the formalin test. In comparison, WKY rats exhibited thermal hyperalgesia in the hot plate test, while behaviour in the tail-flick and von Frey tests did not differ between WKY and Sprague-Dawley rats. Furthermore, WKY rats exhibited enhanced formalin-evoked nociceptive responding up to 40 min post administration, an effect inversely correlated with serotonin and 5-HIAA levels in the hypothalamus. In conclusion, these findings demonstrate that altered pain responding observed in clinically depressed patients can be modelled pre-clinically, providing a means of investigating the neurochemical basis of, and possible treatments for, this phenomenon.
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PMID:Enhanced nociceptive responding in two rat models of depression is associated with alterations in monoamine levels in discrete brain regions. 2095 67


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