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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activation of cardiac sympathetic afferents leads to excitatory cardiovascular reflexes and pain during myocardial ischemia. We hypothesized that cardiac sympathetic afferents are activated by reactive oxygen species produced during ischemia and reperfusion. Single-unit nerve activity of 55 afferents was recorded from the left paravertebral sympathetic chain (T1-T4) in cats anesthetized with alpha-chloralose. Receptive fields of all afferents were located on the right or left ventricle. Mechanical and chemical sensitivities of each afferent ending were evaluated by von Frey hairs, cardiac distension, and local application of bradykinin (BK, 142 pmol) or H2O2 (7.5-15 mumol) to the receptive field. Thirty-one afferents (56%) were responsive to bradykinin (BK), H2O2, and ischemia (2 or 10 min). Deferoxamine (Def, 10-100 mg/kg), dimethylthiourea (DMTU, 10-100 mg/kg), or iron-loaded Def (10 mg/kg) were employed to evaluate the role of H2O2 and hydroxyl radicals (.OH) in activating these afferents (10A delta and 21C fibers) during ischemia and reperfusion. Treatment with the nonspecific scavenger DMTU (n = 10) significantly diminished the increase in discharge activity evoked by ischemia and reperfusion. Treatment with Def also significantly attenuated the responses during ischemia and reperfusion. Thus reactive oxygen species, particularly .OH, activate a group of cardiac sympathetic A delta- and C-fiber afferents during myocardial ischemia and reperfusion and may play an important role in mediating cardiovascular sympathetic reflex responses and/or pain transmission.
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PMID:Ischemia- and reperfusion-sensitive cardiac sympathetic afferents: influence of H2O2 and hydroxyl radicals. 757 32

In seven patients with peripheral neuropathic pain, the effect of systemic adenosine infusion on pain symptoms was evaluated in a double-blind, placebo controlled, cross-over study. The study infusions, adenosine (50 micrograms.kg-1.min-1) or placebo, were given intravenously (IV) during 45-60 min at two separate occasions. Before and during infusions, bedside examination of sensibility and quantitative sensory testing (QST), i.e., assessments of perception thresholds for touch, touch-evoked pain, cold, warmth, painful heat, and cold, were performed. In the neuropathic area, sensation magnitude was rated by a visual analog scale (100 mm VAS) using a pin and at perception threshold for touch-evoked pain using von Frey filaments. Adenosine infusion reduced spontaneous pain (P < 0.05), and caused an increase of the touch-evoked pain threshold from 10.8 +/- 5.3 to 22.2 +/- 6.9 g (P < 0.05), whereas placebo had no effect. Pain intensity at perception threshold for touch-evoked pain was, however, unaltered. Pinprick-evoked pain in the neuropathic areas was reduced from 53 +/- 11 to 29 +/- 10 mm (P < 0.05). No other sensory modality was consistently changed during adenosine infusion. In conclusion, the present study demonstrates that adenosine infusion alleviates spontaneous neuropathic pain, tactile allodynia, and pinprick hyperalgesia in patients with peripheral neuropathic disorders, probably by a central mechanism of action.
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PMID:Systemic adenosine infusion alleviates spontaneous and stimulus evoked pain in patients with peripheral neuropathic pain. 757 99

Intradermal injection of the capsaicin analogue, NE-21610 (Procter and Gamble), inactivates nociceptors but not low-threshold mechanoreceptors in monkey. The present study examined the effects of cutaneous NE-21610 on heat and mechanical sensation in normal human volunteers. In the first series of experiments, subjects received intradermal (i.d.) injections (30 microliters) of the vehicle alone or with the drug (0.3, 3.0, 10 micrograms) into different sites on the volar forearm. Subjects were randomly assigned to 1 of 3 protocols to examine drug-evoked pain (n = 8), or alterations in pain to heat (n = 8) or mechanical (n = 8) stimuli induced by the drug. An additional 7 subjects rated pain to mechanical and heat stimuli before and after subcutaneous (s.c.) injections (300 microliters) of the vehicle or drug (100 micrograms). The peak pain occurred at the time of injection, was of short duration, and was similar for vehicle and drug injections. A mild, dose-related pain followed that lasted up to 2 h. Von Frey thresholds for detection, sharpness, and pain at the injection site (measured 24 h after injection) were not significantly altered by either i.d. or s.c. drug administration. However, pain to stepped heat stimuli was reduced in a dose-dependent fashion for both types of injection. At the highest drug doses, analgesia to heat stimuli was still present 1 week after injection. Recovery of heat sensitivity occurred several weeks after injection. This dissociated loss of heat but not mechanical pain sensibility may be due to: (1) a selective action of the drug on heat transducers in nociceptors responsive to both heat and mechanical stimuli, or (2) a selective action on that subset of nociceptors responsible for signaling heat-evoked pain.
Pain 1995 Apr
PMID:Cutaneous injection of the capsaicin analogue, NE-21610, produces analgesia to heat but not to mechanical stimuli in man. 764 43

This study examined the sensory abnormalities in an unselected, consecutive group of patients with central post-stroke pain (CPSP) surviving more than 1 year after stroke. The sensory examination included clinical examination and quantitative measures with detection and pain thresholds to heat and cold stimuli, argon laser, von Frey hair and determination of stimulus-response function in the 10-45 degrees C range. Sensory examination was in 11 identified CPSP patients (5 female, 6 male; aged 43-80 years) carried out in the painful area using the contralateral homologue area as reference. Pain rating was performed using the McGill Pain Questionnaire and a VAS scale. All patients had ischemic (MRI verified) infarction. Of the 11 patients with supratentorial lesions, 5 had thalamic lesions; in addition, 7 patients had lesions in the brain stem/cerebellum. Median present spontaneous pain intensity on the VAS scale was 3.3 (range: 0-7.7). All patients had pain in the body part with sensory abnormalities, which in 8 patients extended the area with pain. Warm detection threshold was higher in the pain area in all patients, and all except 1 patient had increased cold detection threshold. Cold and heat pain thresholds were raised as well, but to a lesser degree. Sensibility to touch (von Frey hairs) and pain (argon laser) were changed in only 4 and 3 patients, respectively. A stimulus-response curve in the 10-45 degrees C range showed different patterns compared to the non-affected side. A cold allodynia in the 10-45 degrees C range was present in the painful area in 6 (56%) of the patients. The results support the theory that damage to the spino-thalamo-cortical pathway is a necessary condition in CPSP. It is proposed that the spontaneous pain in CPSP is linked to hyperexitability or spontaneous discharges in thalamic or cortical neurons that have lost part of their normal input.
Pain 1995 May
PMID:Sensory abnormalities in consecutive, unselected patients with central post-stroke pain. 765 27

Spinal cord stimulation (SCS) is efficacious for pain due to injury of peripheral nerves, and therefore models of mononeuropathy appear to be particularly suitable for an experimental approach to the study of mechanisms underlying the clinical effect of this mode of treatment in chronic neuropathic pain. Virtually all previous experimental studies on SCS have utilized acute and nociceptive types of peripheral pain stimuli to explore the attenuating effects of SCS. In the present study we made use of the two models of supposedly painful neuropathy developed by Bennett and Xie (1988) and Seltzer et al. (1990) to explore the effect of SCS applied with stimulus parameters similar to those used in clinical practice. In rats subjected to ligatures of the sciatic nerve according to these two methods, SCS was applied via chronically implanted electrodes, or acutely via a laminectomy in the lower thoracic region. In awake, freely moving animals SCS produced a marked increase of the withdrawal thresholds to innocuous mechanical stimuli in the form of von Frey filaments. This threshold elevation lasted for up to 40 min after 10 min of SCS. In about one-half of the animals there was also a moderate, but short-lasting increase in the intact leg. The degree and duration of the withdrawal threshold elevation was clearly related to the intensity of SCS which was kept below the level of which a response in the thoracic or leg musculature was produced. In a second series of experiments the effect of SCS, applied acutely via a laminectomy, on the early component (latency: 8-12 msec) of the flexor reflex was studied. As a result of nerve ligation with either of the methods used, the thresholds for evoking the early as well as the late component in the nerve-ligated leg were significantly lower than in the intact one. SCS resulted in a marked and long-lasting increase of the threshold of the early component in the nerve-ligated leg. On the intact side only a slight and short-lasting increase was observed. The late, C fibre-mediated component was not influenced by SCS. The first component of the flexor reflex is conceivably mediated by A beta-fibre activation and it presumably corresponds to the withdrawal response induced by innocuous mechanical stimuli. The lack of effect of SCS on the late reflex component indicates that it selectively influences transmission of A-fibre activity. (ABSTRACT TRUNCATED AT 400 WORDS)
Pain 1995 May
PMID:Spinal cord stimulation in animal models of mononeuropathy: effects on the withdrawal response and the flexor reflex. 765 33

Peripheral neuropathy can be associated with a variety of symptoms, including spontaneous unpleasant sensations and pain, as well as increased sensitivity to sensory stimuli. A peripheral neuropathy model involving an L5 spinal nerve lesion in male rats has been used to gain insight into the mechanisms that underlie symptoms that develop after nerve injury. This model was used to study the involvement of sensory fibres, the sympathetic postganglionic neuron and the role of nerve growth factor in the induction and maintenance of altered sensory function in the nerve territory of the intact L4 spinal nerve. Sensory testing was done with calibrated von Frey filaments and a radiant heat apparatus [Hargreaves K. et al. (1988) Pain 32, 77-88] and the occurrence of abnormal spontaneous behaviour was recorded. L5 spinal nerve resection produced increased mechanical and heat sensitivity as well as abnormal spontaneous behaviours. Surgical sympathectomy at the L5 but not at the L4 spinal nerve level alleviated all sensory abnormalities. However, a lesion of preganglionic fibres to the L5 level had no significant effect on sensory abnormalities. Thus, sympathetic postganglionic neurons at the level of spinal nerve injury can contribute to neuropathy symptoms independent of input from preganglionic neurons. Postganglionic sympathetic nerve crush alone led to increased mechanical sensitivity but not to increased heat sensitivity nor to abnormal spontaneous behaviour, further emphasizing the role of sympathetic postganglionic neuron changes for the development of increased mechanical sensitivity. An L5 spinal nerve resection in rats treated neonatally with capsaicin induced increased mechanical sensitivity which was slower in onset and lower in magnitude than that in untreated littermates and was abolished by postganglionic sympathectomy. Nerve growth factor perfused onto the cut L5 spinal nerve also markedly delayed the onset of increased mechanical sensitivity. Two pathophysiological mechanisms leading to central changes may be necessary to produce altered sensations in this model: (i) ongoing activity in C-fibres, independent of sympathetic postganglionic neuron activity and (ii) activity in sensory fibres modulated by a sensory-sympathetic interaction in the injured spinal nerve or dorsal root ganglion. The sympathetic postganglionic neuron contribution is independent of preganglionic sympathetic outflow from the central nervous system, suggesting a novel mechanism by which sympathetic efferent terminals can regulate sensory fibre activity. A contribution of a loss of neurotrophic factors to the sympathetic postganglionic neuron following nerve lesion is also suggested to contribute to the symptoms induced by the spinal nerve lesion.
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PMID:Sensory and sympathetic contributions to nerve injury-induced sensory abnormalities in the rat. 771 84

Pre-emptive treatment with an i.v. infusion of morphine 10 mg at induction reduces postoperative analgesic requirement and wound hypersensitivity compared with the same dose administered at the end of operation. Increasing the dose of preemptive morphine may potentially reduce postoperative pain further, while administering morphine at the end of operation, in addition to the beginning, may reduce pain generated by the sensory activity elicited from the wound in the immediate postoperative period. To examine this we have conducted a randomized, double-blind study in patients undergoing abdominal hysterectomy to compare the effect of morphine 20 mg administered before operation with 10 mg at induction and 10 mg on closure of the peritoneum. Postoperative pain was assessed by visual analogue score (VAS) at rest and on movement and by total morphine consumption administered by patient-controlled analgesia (PCA). Wound sensitivity was assessed by von Frey pain thresholds. Both groups had similar morphine consumption, VAS scores and touch and pain thresholds, and in both, secondary hyperalgesia was prevented. Nausea and vomiting scores were higher in the 20-mg group. There was no significant difference between the two groups and neither regimen appeared to offer obvious clinical advantages compared with a lower dose (10 mg) morphine analgesic strategy. Therefore, there may be a ceiling effect to the production of pre-emptive analgesia by morphine.
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PMID:Is there any clinical advantage of increasing the pre-emptive dose of morphine or combining pre-incisional with postoperative morphine administration? 773 57

A comparison study was conducted to determine if a gender difference could be detected using an animal model for causalgia. The sciatic nerve was tightly ligated so that 1/3 to 1/2 of the nerve thickness was trapped by the ligature, just distal to the point at which the posterior biceps semitendinosus nerve branches off the common sciatic nerve. By measuring paw withdrawal from innocuous stimulation with Von Frey filaments, the percent of rats displaying average mechanical sensitivity of the injured paw that was significantly elevated compared to sham or unoperated control animals (days 22-24) was 28.6% for the male group versus 63.6% for the female group. Our animals did not display a consistent response in withdrawal latency to heat applied to the plantar surface of the root (hyperpathia). The data suggests that female rats are significantly more susceptible to developing neuropathic pain than male rats using this experimental model for causalgia.
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PMID:Female rats are more susceptible to the development of neuropathic pain using the partial sciatic nerve ligation (PSNL) model. 777 82

We investigated the role of capsaicin-sensitive small diameter fibers in the development of the thermal and mechanical allodynia in a new rat model for neuropathic pain, produced by transecting some but not all of the nerves innervating the tail. Capsaicin (50 mg/kg, s.c.) injected neonatally prior to the nerve injury produced thermal hypoalgesia in the tail the degree of which was variable across individual rats, presumably as a result of variable degeneration of the small diameter fibers. When subjected to the nerve injury, the animals with moderate thermal hypoalgesia exhibited signs of pain (e.g., tail flick) to normally innocuous mechanical stimuli applied to the tail with von Frey hairs (4.9 mN or 19.6 mN bending force), but not to thermal stimuli given by immersion of the tail into cold (4 degrees C) or warm (40 degrees C) water. The animals with marked thermal hypoalgesia, on the other hand, exhibited no signs of pain either to the mechanical or to the thermal stimuli. These results suggest that the capsaicin-sensitive fibers are critical in the development of both the mechanical and thermal allodynia. It is hypothesized that the destruction of A delta- and C-nociceptive fibers by capsaicin prevented activities induced in these fibers by the nerve injury from producing a central sensitization and thus allodynia.
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PMID:Critical role of the capsaicin-sensitive nerve fibers in the development of the causalgic symptoms produced by transecting some but not all of the nerves innervating the rat tail. 779 Sep

We have previously introduced a novel animal model of neuropathic pain in rats following a peripheral mononeuropathy produced by freezing the common sciatic nerve, a technique termed sciatic cryoneurolysis (SCN). In this study, we have further characterized the temporal pattern of behavioral changes following SCN, including thermal hyperalgesia and mechanical allodynia. These behaviors were assessed using noxious thermal (radiant heat) and non-noxious tactile (von Frey filament) stimuli, respectively. Following unilateral SCN, animals exhibited significant (P < 0.001) bilateral tactile hypersensitivity (allodynia) that persisted at least 10 weeks. However, this lesion did not result in thermal hypersensitivity (hyperalgesia). In fact, thermal sensitivity in the operated limb remained significantly suppressed throughout the 10 weeks (P < 0.001). Furthermore, we observed autotomy in 76% of SCN-lesioned animals as well as transient weight loss and pale eye syndrome (PES), a phenomenon previously unreported in other neuropathic pain models. PES is a sustained, visibly distinct pallor of the normally pink eye color of the albino rat. We believe PES is a putative marker of heightened sympathetic efferent activity. The severity of autotomy following SCN correlated significantly with both weight loss (P < 0.001) and the expression of PES (P < 0.001). Autotomy behavior preceded the onset of allodynia; however, there was no correlation between the severity of expression of these behaviors. These behavioral sequelae are comparable to those seen in other animal models of neuropathic pain, but differ in respect to the increased frequency of autotomy and the lack of thermal hyperalgesia.(ABSTRACT TRUNCATED AT 250 WORDS)
Pain 1994 Aug
PMID:Differential behavioral outcomes in the sciatic cryoneurolysis model of neuropathic pain in rats. 781 82


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