Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162473 (Frey)
 2,599 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine whether tactile sensitivity of the normal skin is altered by suppression of sympathetic efferent activity, the effect of stellate ganglion block and epidural sympathetic block on touch threshold was studied. The study was performed on ten individuals with various chronic pain syndromes. Tactile sensitivity was measured in the normal skin area with the use of von Frey filaments and a two-alternative forced-choice procedure with a staircase presentation of touch stimuli. With stellate ganglion block, touch threshold decreased on the side of the block by 48.8 +/- 8.% (P = 0.002) without any significant change in the threshold on the healthy, nonblocked side (P = 0.003 for the difference between the sides). With epidural sympathetic block, touch threshold decreased to the same extent on the diseased and healthy sides, which were both affected by the block (46.2 +/- 11.4%, P = 0.027 and 47.7 +/- 12.5%, P = 0.032, respectively). The results show that sympathetic blockade increases tactile sensitivity. They also suggest that sympathetic efferent activity modulates the function of tactile receptors. It is hypothesized that the sympathetic modulation makes tactile receptors less sensitive to touch, less specific, and probably more prone to code tactile stimuli in such a way that the brain recognizes this code as pain.
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PMID:Sympathetic blockade increases tactile sensitivity. 368 97

Rheumatoid arthritis (RA) is characterised by pain and tenderness not only over inflamed or damaged joints, but also over apparently normal tissues. Experimental models suggest that these features results from changes of sensitivity within both peripheral and central neurones, but direct evidence from human disease is lacking. At present, most clinical studies have evaluated overall pain experience rather than activity within components of the nociceptive pathway. Therefore, the aim of this study was to assess the use of a capsaicin-based technique to quantify changes of neuronal sensitivity in patients with RA. First 20 microliters of capsaicin in solution (0.03 mg/ml) was applied topically for 30 min to apparently normal skin on the forearm of control subjects and patients with RA. The subsequent development of mechanical hyperalgesia to pinprick stimuli was then measured at various time points using a 74.4-mN von Frey hair. The relationship between the area of hyperalgesia and a number of clinical measures was determined. Capsaicin-induced mechanical hyperalgesia was found to decline with age in normal subjects (r = 0.47, P < 0.01). The development of hypearlgesia had a similar time course in normal subjects and patients with RA. The maximum area of hyperalgesia, however, was substantially larger in 35 RA patients; 254.3 +/- 20.7 cm2, compared with 35 normal controls; 109 +/- 7.5 cm2 (P < 0.001). An association was apparent between hyperalgesic area and a composite score of joint tenderness (r = 0.47, P < 0.01), but not with overall pain score or a systemic marker of inflammation. These results provide evidence for enhanced sensitisation of a population of sensory fibres in RA. Peripheral sensory activity over the forearms of rheumatoid patients has previously been shown to be normal and the results suggest the presence of enhanced central mechanisms in this disorder. The correlation between capsaicin-induced hyperalgesia and joint tenderness in the RA patients implies that joint symptoms arise partially as a result of central, and not exclusively peripheral, factors. The study supports the use of capsaicin-based techniques to explore nociceptive mechanisms in clinical disorders characterised by chronic pain.
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PMID:Characterisation of capsaicin-induced mechanical hyperalgesia as a marker for altered nociceptive processing in patients with rheumatoid arthritis. 921 79

Spinal cord N-methyl-D-aspartate (NMDA) receptors play an important role in the transmission of acute and chronic pain. The present study investigated the ability of dextrorphan (DEX), a metabolite of dextromethorphan and a clinically safe NMDA antagonist, to attenuate the responses of nociceptive spinothalamic tract (STT) neurons in anesthetized monkeys. The STT cells were recorded extracellularly in the lumbosacral enlargement and were identified by antidromic activation from the ventral posterior lateral thalamic nucleus. DEX administered through a microdialysis fiber inserted into the dorsal horn inhibited the responses of STT cells in normal animals to noxious pinch and heat stimuli. In monkeys made neuropathic by tight ligation of the L7 or S1 spinal nerve, DEX significantly attenuated the responses of STT cells to noxious pinch and heat, as well as to innocuous brushing, pressure and von Frey filament stimuli. These findings strongly suggest that DEX should be considered a potentially useful therapeutic agent for the treatment of neuropathic pain in humans.
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PMID:Dextrorphan attenuates responses of spinothalamic tract cells in normal and nerve-injured monkeys. 923 85

Spinal cord injury (SCI) results in variable motor recoveries and chronic central pain syndromes develop in the majority of SCI patients. To provide a basis for further studies, we report a new rodent model of chronic central pain following spinal cord trauma. Male Sprague-Dawley rats (N = 10) were hemisectioned at T13 and were tested both preoperatively and postoperatively and compared to sham-operated controls (N = 10) for locomotor function, and mechanical and thermal thresholds of both paw withdrawal and supraspinal responses. Results support the development and persistence of allodynia which persists for 160 days. Locomotor function was tested using the Basso, Beattie and Bresnahan (BBB) open field test and only the limb ipsilateral to the hemisection was affected, demonstrating acute flaccid paralysis with motor recovery which approached normal values by postoperative day (POD) 15. Prior to the hemisection, the rats showed little to no paw withdrawal response to von Frey stimulation of 4.41 mN or 9.41 mN in both forelimbs and hindlimbs. Postoperatively, responses in both ipsilateral and contralateral forelimbs and hindlimbs increased over time and the increase was statistically significant compared to intra-animal presurgical and sham control values (P < 0.05). There were no significant side-to-side differences in limb responses preoperatively or beyond POD 15. The forelimbs and hindlimbs responded to von Frey hair strengths of 122 mN preoperatively and postoperatively with similar withdrawal frequencies that were not statistically significant. Preoperatively, the paw withdrawal latency to heat stimuli was 22.9 +/- 3.0 (mean +/- SE) and 20.1 +/- 3.1 sec for the hindlimbs and forelimbs, respectively. Postoperatively, the mean hindlimb and forelimb latency of paw withdrawals decreased to 11.9 +/- 1.8 and 9.2 +/- 2.5 sec, respectively. This decrease in thermal thresholds is statistically significant when compared to intra-animal preoperative and sham control values (P < 0.05). These data indicate that somatosensory thresholds for non-noxious mechanical and radiant heat which elicit paw withdrawal (flexor reflex) are significantly lowered following SCI. To further support the development and persistence of chronic pain following hemisection, supraspinal responses such as paw lick, head turns, attacking the stimulus, and vocalizations were elicited in response to mechanical and thermal stimuli and were statistically significant compared to presurgical intra-animal or sham control values (P < 0.05). Hemisected animals vocalized to von Frey hair bending forces of 49.8 with a mean of 6.0 +/- 1.2 times out of 10 stimuli compared to intra-animal presurgical and sham control values of zero. Supraspinal responses of hemisected animals to thermal stimuli occurred at lower temperatures that were statistically significant compared to sham control or preoperative values (P < 0.05). These chronic changes in thresholds to both mechanical and thermal stimuli represent the development and persistence of mechanical and thermal allodynia after SCI.
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PMID:Mechanical and thermal allodynia in chronic central pain following spinal cord injury. 925 4

Nerve growth factor (NGF) induces a relatively long-term hyperalgesia in rats, whereas substance P (SP) N-terminal fragments, like SP(1-7), produce a long-lasting antinociception in mice. We used various nociceptive assays to compare the effects of these compounds on pain transmission when injected intrathecally (i.t.) in mice, and to determine whether either compound affects the action of the other. NGF produced thermal hyperalgesia when injected i.t. in mice 24 and 48 hr before testing by the tail-flick assay. During this same interval, NGF elicited no effect on the response to von Frey fibers or on chemically induced nociception measured by the writhing assay. In contrast to NGF, SP(1-7) had no effect on tail-flick latencies but induced antinociception in the writhing assay 24 hr after injection. When administered 2 hr before NGF, SP(1-7) antagonized the thermal hyperalgesic effect of NGF in a dose-related fashion, despite the inability of SP(1-7) to alter tail-flick latency when administered alone. NGF, in turn, antagonized the antinociceptive effects of SP(1-7) in the writhing assay. The D-amino acid-substituted analog, D-SP(1-7), failed to mimic the antinociceptive effect of SP(1-7) or to alter the hyperalgesic effect of NGF, which indicated a stereoselective action of SP(1-7). D-SP(1-7), that inhibits SP(1-7) binding, did reverse the ability of SP(1-7) to antagonize NGF-induced hyperalgesia, consistent with its action as a SP N-terminal antagonist. Mutual antagonism between NGF and SP may reflect modulatory roles of these endogenously occurring peptides during chronic pain when N-terminal metabolites of SP may accumulate.
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PMID:Mutual antagonism between nerve growth factor and substance P N-terminal activity on nociceptive activity in mice. 931 45

We have used a partial nerve ligation model of chronic pain to investigate if there are changes in the expression of mRNA for several immediate early genes (IEG) that correlate in time with the initial adaptive behavioural changes and with development of allodynia in this model. The animals were inspected for typical changes in posture, and mechanical allodynia was evaluated using von Frey filaments. Expression of three of the immediate early genes examined, c-fos, NGFI-A and jun B, was transiently increased in the ipsilateral dorsal horn of the spinal cord following the partial ligation of the sciatic nerve. The time course and extent of these changes were similar to those reported for acute noxious stimuli. c-jun mRNA expression was significantly enhanced, after a delay of more than 12 h, and then remained elevated over the entire studied period of 4 weeks. These changes occurred only in the ventral horn, particularly in lamina IX. Except for c-jun mRNA, all changes were transient despite behavioural evidence for continuing allodynia. These results from the partial nerve ligation model, when compared with results obtained using other models of acute or chronic nerve injury, suggest that the immediate early genes we have examined are not sufficient to explain the transition to chronic pain states. The results also show that in this model of chronic pain there are prolonged adaptive changes in motor neurons and that these changes are temporally associated with the development of chronic pain and allodynia.
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PMID:Spinal expression of mRNA for immediate early genes in a model of chronic pain. 942 60

Neurotropin is commonly used in Japan for the treatment of chronic pain. Using a rat model, we evaluated the effect of neurotropin on a unilateral peripheral mononeuropathy produced by placing loose ligatures around the sciatic nerve. The effect of neurotropin upon the resultant hyperalgesia and mechanical allodynia was assessed using the Ugo Basile Plantar test and von Frey hairs test, respectively. Neurotropin reduced thermal hyperalgesia and produced an early recovery from hyperalgesia in a dose-dependent manner. No significant reduction in mechanical allodynia, however, was noted under the tested condition. A possibility of differential drug sensitivity for thermal hyperalgesia and mechanical allodynia was indicated in this model, although the reason still remain elusive.
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PMID:Effects of neurotropin on hyperalgesia and allodynia in mononeuropathic rats. 982 71

Injury to peripheral nerves often results in chronic pain which is difficult to relieve. The mechanism underlying the pain syndrome remains largely unknown. In previous studies we showed that neurotrophins are up-regulated in satellite cells around sensory neurons following sciatic nerve lesion. In the present study, we have examined whether the neurotrophins in the dorsal root ganglia play any role in allodynia after nerve injury. Antibodies to different neurotrophins, directly delivered to injured dorsal root ganglia, significantly reduced (with different time sequences) the percentage of foot withdrawal responses evoked by von Frey hairs. The antibodies to nerve growth factor acted during the early phase but antibodies to neurotrophin-3 and brain-derived neurotrophic factor were effective during the later phase. Exogenous nerve growth factor or brain-derived neurotrophic factor, but not neurotrophin-3, directly delivered to intact dorsal root ganglia, trigger a persistent mechanical allodynia. Our results showed that neurotrophins within the dorsal root ganglia after peripheral nerve lesion are involved in the generation of allodynia at different stages. These studies provide the first evidence that ganglia-derived neurotrophins are a source of nociceptive stimuli for neuropathic pain after peripheral nerve injury.
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PMID:Neurotrophins from dorsal root ganglia trigger allodynia after spinal nerve injury in rats. 1065 64

It is well recognized that gender differences play a major role in pain sensitivity, pain report, analgesic efficacy and prevalence of certain chronic pain disorders. In the present study we sought to determine whether male or female rats of two different outbred strains (Sprague-Dawley and Holtzman) experienced differential pain sensitivity after the same mononeuropathy lesion. Following baseline mechanical allodynia testing, rats of each sex and strain underwent an L5 spinal nerve transection. Mechanical allodynia using 2 and 12 g von Frey filaments was assessed at days 1, 3, 5, 7, and 10 post surgery. There were no statistically significant differences in allodynia between gender in the Holtzman strain or between strains. However, mechanical allodynia was significantly greater in female Sprague-Dawley rats as compared with males following a spinal nerve transection. These data suggest that the choice of rat gender and strain should be considered in experimental neuropathic pain studies, especially in the assessment of potential analgesics.
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PMID:Gender differences in rat neuropathic pain sensitivity is dependent on strain. 1071 25

Mice lacking the gene encoding for substance P and neurokinin A, or the NK-1 receptor, exhibit alterations in behavior to various acute nociceptive stimuli. However, behavioral responses of NK-1 mutant animals have not been well characterized in models of chronic pain. We studied the behavioral responses of NK-1 knockout and wild-type control mice to thermal and mechanical stimuli before and after inducing chronic neuropathic pain by unilateral ligation of the L5 spinal nerve. Mechanical hyperalgesia was evaluated by determining the frequency of withdrawal to von Frey monofilaments applied to the hind paws. Nerve injury-induced hyperalgesia to thermal stimuli was examined by determining responses to radiant heat and cooling stimuli. The contribution of the sympathetic nervous system to mechanical hyperalgesia was evaluated by administering 3 mg/kg phentolamine, an alpha-adrenergic antagonist, subcutaneously. Following spinal nerve injury, withdrawal frequencies to mechanical stimulation increased in wild-type mice within 1 day and persisted during the 9-week observation period, whereas in the knockout mice, withdrawal frequencies did not increase significantly. In contrast, withdrawal latencies to radiant heat decreased up to 2 weeks after nerve injury in both the NK-1 and the wild-type mice. Similarly, the increase in withdrawal frequency to the cooling stimuli following the nerve injury was not different in the NK-1 knockout and wild-type mice. Mechanical hyperalgesia in the wild-type mice was not reversed by systemic administration of phentolamine, suggesting that the pain is not sympathetically maintained. The results indicate that NK-1 receptors contribute to the development of mechanical, but not thermal, hyperalgesia in neuropathic pain.
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PMID:Nerve injury-induced mechanical but not thermal hyperalgesia is attenuated in neurokinin-1 receptor knockout mice. 1073 40


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