Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A German shepherd dog was treated initially for signs of urinary tract infection; subsequently, signs of spinal pain and neurologic deficits developed. Fungal hyphae were found in the urine sediment, and spinal radiography revealed changes in the vertebrae and intervertebral disks at the levels of T3 to T8, T12 to T13, L3-4, and L5-6, consistent with diskospondylitis. Fungal cultures of urine and specimens from spinal lesions yielded Aspergillus terreus. Itraconazole (5 mg/kg of body weight, PO, q 24 h) was used to treat this infection, and locomotion improved. Sudden death occurred 4 weeks after treatment was initiated; this was attributed to exsanguination associated with a weakened renal artery. This dog was raised in Florida and resided in central Virginia. The disseminated aspergillosis found in this dog was not limited to the hot arid climates that some reports suggest are optimal conditions for growth.
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PMID:Disseminated aspergillosis in a dog with diskospondylitis and neurologic deficits. 155 89

Recordings were made from 68 units in the nucleus ventralis posterolateralis (VPL) of the cat thalamus, which responded to stimulation of hypogastric afferents. These units also received nociceptive inputs from the contralateral integument. Units which responded exclusively to hypogastric afferent inputs were not found. Thirty seven of the units were nociceptive specific (NS), and the remaining 31 were wide dynamic range (WDR) units. All of these units were located in the shell region of the lateral subdivision of the caudal VPL. NS units responding to hypogastric afferent inputs had a circumscribed cutaneous receptive field on the contralateral abdomen, gluteal region, tail or hind limb. These areas corresponded to tactile dermatomes T13-S2. Similarly, the cutaneous receptive fields of WDR units receiving hypogastric afferent inputs were distributed in the contralateral abdomen, gluteal region, tail and hind limb, with the sole exception of one unit, whose receptive field also included a part of the lower thorax. These findings extend the previous findings that the shell region of the caudal VPL of the cat thalamus constitutes a thalamic link in a visceral pain pathway, and that the visceral and cutaneous pathways share a common projection locus in the VPL.
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PMID:Responses of neurons in nucleus ventralis posterolateralis of the cat thalamus' to hypogastric inputs. 274 9

Neurons receiving cardiac sympathetic afferent input were studied in the nucleus ventralis posterolateralis (VPL) of the cat thalamus. Animals were anesthetized with urethan-chloralose. Units in the VPL were classified into 3 classes; low-threshold mechanoreceptive (LTM), nociceptive specific (NS) and wide dynamic range (WDR) units. Units driven by electrical stimulation of the left inferior cardiac nerve (ICN) were not included in the population of LTM units, but 43.5% of NS units and 68.8% of WDR units were excited by this stimulation. Units exclusively responsive to cardiac sympathetic afferents were not found. Both NS and WDR units were located in the shell region of the caudal VPL. NS units responsive to cardiac sympathetic afferents had a circumscribed cutaneous receptive field in the area corresponding to tactile dermatomes C5-T13. WDR units receiving cardiac sympathetic afferent input had at least a part of their receptive fields in the same area. These results suggest that the shell region of the caudal VPL constitutes a thalamic link in a cardiac pain pathway, and that cardiac and cutaneous pain systems share a common projection locus in the VPL.
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PMID:Cardiac sympathetic afferent input onto neurons in nucleus ventralis posterolateralis in cat thalamus. 343 26

Forty-four rats were subjected to unilateral intradural section of dorsal roots T13-L6. Of these, 10 were housed alone and 34 were housed with female rats. Each of the 10 animals housed alone-self-mutilated to an extreme degree, with 7 cannibalizing the denervated limb. Only of the animals housed with a female showed any sign of self-biting, and this was a minor, isolated incident. These results are discussed with particular reference to dorsal rhizotomy in rats serving as a model of chronic pain.
Pain 1982 Jul
PMID:The influence of housing condition on autotomy following dorsal rhizotomy in rats. 688 23

Dorsal column stimulation (DCS) is used clinically to provide pain relief from peripheral vascular disease and has the benefit of increasing cutaneous blood flow to the affected lower extremities. The purpose of this study was to examine the role of dorsal roots, calcitonin gene-related peptide (CGRP), and substance P in the cutaneous vasodilation induced by DCS. Male rats were anesthetized with pentobarbital sodium (60 mg/kg ip). A unipolar ball electrode was placed unilaterally on the spinal cord at the L1-L2 spinal segment. Blood flow was recorded in each hindpaw foot pad with laser Doppler flowmeters. Blood flow responses were assessed during 1 min of DCS (either 0.2 mA subdural or 0.6 mA epidural at 50 Hz, 0.2-ms pulse duration). Dorsal rhizotomy of L3-L5 (n = 5) abolished the cutaneous vasodilation to subdural DCS, whereas removal of T10-T12 (n = 5) and T13-L2 dorsal roots (n = 5) did not attenuate the DCS-induced vasodilation. The CGRP antagonist, CGRP-(8-37) (2.6 mg/kg iv, n = 7), eliminated the epidural DCS-induced vasodilation, whereas the substance P receptor antagonist, CP-96345 (1 mg/kg iv, n = 6), had no effect. In summary, L3-L5 dorsal roots and CGRP are essential for the DCS-induced vasodilation. We propose that DCS antidromically activates afferent fibers in the dorsal roots, thus causing peripheral release of CGRP, which produces cutaneous vasodilation.
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PMID:Cutaneous vasodilation during dorsal column stimulation is mediated by dorsal roots and CGRP. 912 59

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.
Pain 1996 Nov
PMID:Mechanical and thermal allodynia in chronic central pain following spinal cord injury. 925 4

Expression of bradykinin receptors was analyzed in freshly isolated dorsal root ganglion neurons of the ipsi- and contralateral segments L4/L5, L2/L3, and T12/T13 two to twenty days after unilateral injury of the adult rat sciatic nerve using gold labeled bradykinin. The number of infiltrating leucocytes was investigated by flow cytometry. Sciatic nerve injury transiently increased the proportion of neurons expressing bradykinin receptors not only in the ipsilateral ganglia L4/L5, but also in the homonymous contralateral ganglia and also bilaterally in the adjacent ganglia L2/L3. Neurons of the ganglia T12/T13 were not affected. The time course of upregulation was different between neurons of the injured nerve and uninjured ones. Furthermore, the proportion of neurons expressing a high density of receptors increased also bilaterally in ganglia L4/L5 and L2/L3. As on the ipsilateral side, the increase in neurons expressing bradykinin receptors in the contralateral homonymous ganglia was due to an induction of the B1 receptor subtype and an upregulation of the B2 subtype. As a possible source for stimulating factors for induction of bradykinin receptors the number of macrophages and lymphocytes was investigated two to twenty days after nerve ligation. No increase was observed prior to day ten and only in ipsilateral ganglia L4/L5, not contralaterally and not in adjacent ganglia L2/L3 and T12/T13. The experiments show that the induction of bradykinin receptors following a unilateral nerve lesion is not restricted to neurons projecting into the damaged nerve but is (i) bilateral, (ii) different in time course between injured and uninjured neurons, and (iii) locally confined to neurons of the adjacent ganglia. Macrophages and lymphocytes are increased after ten day ligation only in the affected ganglia and are probably not involved in the induction of bradykinin receptors.
Pain 1999 Dec
PMID:Spatio-temporal pattern of induction of bradykinin receptors and inflammation in rat dorsal root ganglia after unilateral nerve ligation. 1056 57

CGRP(8-37) is a truncated version of calcitonin gene-related peptide (CGRP) that binds to the CGRP receptor with similar affinity but does not activate the receptor and is a highly selective CGRP receptor antagonist. CGRP and activation of its receptor appear to play a role in peripheral inflammatory and neuropathic models of pain although there is considerable controversy. The aim of this study was to examine possible anti-nociceptive effects of CGRP(8-37) on a model of chronic central neuropathic pain known to develop weeks after spinal hemisection. Adult male Sprague-Dawley rats were given a spinal hemisection (N=34) or a sham surgery (N=10) at the T13 spinal segment. An externally accessible PE-10 intrathecal catheter that terminated at T13 was used for drug delivery. Animals were allowed to recover for 4 weeks at which time the hemisected animals displayed mechanical and thermal allodynia bilaterally, in both forelimbs and hindlimbs. CGRP(8-37) was delivered just prior to a testing session in 1, 5, 10, or 50 nM doses in artificial cerebral spinal fluid in 10 microl volumes. CGRP(8-37) was effective in alleviating mechanical and thermal allodynia in a dose-dependent manner (P<0.05). The 50 nM dose was most efficacious for both forelimb and hindlimb responses (P<0.05). The period of efficacy was 10 min to onset for a duration of 20 min. Post-drug washout responses were not statistically significant compared to pre-drug responses. The sham control groups demonstrated no statistically significant difference at any dose of CGRP(8-37) when compared to pre-surgical baseline values. In conclusion, CGRP(8-37) is effective in abolishing mechanical and thermal allodynia produced by spinal hemisection. Consequently, the CGRP receptor may play a role in chronic central neuropathic pain and offers a novel therapeutic approach to managing chronic central pain.
Pain 2000 May
PMID:Alleviation of mechanical and thermal allodynia by CGRP(8-37) in a rodent model of chronic central pain. 1077 73

In the majority of patients, spinal cord injury (SCI) results in abnormal pain syndromes in which non-noxious stimuli become noxious (allodynia). To reduce allodynia, it would be desirable to implant a permanent biological pump such as adrenal medullary chromaffin cells (AM), which secrete catecholamines and opioid peptides, both antinociceptive substances, near the spinal cord. We tested this approach using a recently developed a mammalian SCI model of chronic central pain, which results in development of mechanical and thermal allodynia. Thirty day-old male Sprague-Dawley rats were spinally hemisected at T13 and allowed 4 weeks for recovery of locomotor function and development of allodynia. Nonimmunosuppressed injured animals received either control-striated muscle (n = 7) or AM (n = 10) transplants. Nociceptive behavior was tested for 4 weeks posttransplant as measured by paw withdrawals to von Frey filaments, radiant heat, and pin prick stimuli. Hemisected animals receiving AM demonstrated statistically significant reductions in both fore- and hindlimb mechanical and thermal allodynia, but not analgesia, when compared to hemisected animals receiving striated muscle transplants (P < 0.05). Tyrosine hydroxylase immunoreactivity indicated prolonged transplant survival and production of catecholamines. HPLC analysis of cerebrospinal fluid samples from animals receiving AM transplants demonstrated statistically significant increases in levels of dopamine (sevenfold), norepinephrine (twofold), and epinephrine (threefold), compared to control values several weeks following transplant (P < 0.05). By 28 days posttransplant, however, antinociceptive effects were diminished. These results support the therapeutic potential of transplanted AM in reducing chronic central pain following spinal cord injury.
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PMID:Transplants of adrenal medullary chromaffin cells reduce forelimb and hindlimb allodynia in a rodent model of chronic central pain after spinal cord hemisection injury. 1091 81

Spinal cord injury (SCI) results in loss of locomotor function and development of abnormal chronic pain syndromes (mechanical allodynia, thermal hyperalgesia). Following injury, secondary mechanisms including release of excitatory amino acids, inflammation and lipid peroxidation damage neural cells through release of cytotoxic free radicals. We hypothesized that selective inhibition of cyclooxygenase-2 (COX-2), an inducible inflammatory mediator, would decrease tissue damage and subsequently reduce locomotor deficits and development of chronic central pain syndromes after injury. Fifteen minutes prior to receiving T13 spinal segment spinal cord contusion injury, 200-225-g male Sprague-Dawley rats received either vehicle (0.5 ml 1:1 v/v DMSO/saline, i.p., n = 20) or the selective COX-2 inhibitor NS-398 (5 mg/kg in DMSO/saline v/v, i.p., n = 20). Locomotor function via the BBB scale, and nociceptive behaviors measured by paw withdrawals to von Frey filaments and radiant heat stimuli were tested for 4 weeks postinjury. Histological examination and volumetric analysis of spinal cord tissue were performed concomitantly. Spinally contused animals receiving NS-398 demonstrated significantly (p < 0.05) reduced locomotor alteration and reductions in both fore- and hindlimb mechanical allodynia and thermal hyperalgesia when compared to vehicle controls. Histological examination of spinal segments at the lesion segment demonstrated reduced lesion extent and increased viable tissue when compared to vehicle controls. Prostaglandin E2 levels were significantly lowered in NS-398-treated but not vehicle-treated animals 12 h after injury. These results support the role of COX-2 in reducing pathological and behavioral deficits after spinal cord injury.
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PMID:Reduction of pathological and behavioral deficits following spinal cord contusion injury with the selective cyclooxygenase-2 inhibitor NS-398. 1133 42


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