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

The effects of selective manipulations of activity of the serotonergic and noradrenergic systems were examined in the rat model of visceral pain. It was found that neither p-chlorophenylalanine(p-CPA)- nor N-chloro-ethyl-2,2--bromo-benzylamine(DSP-4)-induced strong and selective depletion of the brain and spinal cord serotonin and noradrenaline, respectively, changed in a significant way rat visceral pain perception. On the other hand, 8-OH-DPAT, a full selective 5-HT1A receptor agonist, prazosin, an alpha1-adrenoceptor antagonist, clonidine, an alpha2-adrenoceptor agonist, and two beta-adrenoceptor antagonists: propranolol and metoprolol, dose-dependently reduced the number of body writhes induced by intraperitoneally administered 2% solution of acetic acid (the writhing test). The results obtained with selective receptor ligands, DSP-4 and p-CPA, indicate that the noradrenergic and serotonergic innervation of the central nervous system contribute in a complex way to the animal behavior in the writhing test. The 5-HT1A receptors and alpha2-adrenoceptors play an inhibitory role in the expression of rat behavior in this model of visceral pain. On the other hand, adrenergic alpha1 and beta1 receptors facilitate the behavioral effects of the irritant agent.
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PMID:Role of serotonergic and noradrenergic systems in a model of visceral pain. 1199 65

A 49-year-old female underwent bilateral breast preserving surgery for heterochronic breast cancers. She later developed a sternal metastasis and was recommended for intravenous chemotherapy. However, she refused such an intensive therapy and opted for immunotherapy. Afterward, she came to our hospital because of spinal metastases with back pain. She was treated with oral administration of 5'-DFUR and MPA 1,200 mg/day for 3 weeks, respectively, CPA 100 mg/day for 2 weeks, and pamidronate disodium 30 mg intravenously every 4 weeks. This combined chemotherapy relieved her pain after one course. After 5 courses, tumor markers were reduced to the normal range. After 14 courses, bone X-P revealed that the osteolytic bone showed sclerotic changes and bone scintigraphy showed a complete remission (CR). The adverse effects were not remarkable. This regimen is possible on an outpatient basis, and it may play an important role from the standpoint of treatment effectiveness and the quality of life of the patient.
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PMID:[A case of breast cancer with multiple bone metastases that responded remarkably to doxifluridine (5'-DFUR), cyclophosphamide (CPA), medroxyprogesterone acetate (MPA) and pamidronate disodium therapy]. 1204 Jun 86

Hyperalgesia and altered activities of enzymes involved in nucleotide hydrolysis are observed after exposure to repeated restraint in rats. Here, we investigated the effect of an adenosine A(1) receptor agonist, N(6)-cyclopentyladenosine (CPA, 3.35 mg/kg, i.p.), adenosine A(1) receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 0.8 mg/kg, i.p.) as well the effect of an adenosine reuptake blocker, dipyridamole (5 mg/kg, i.p.), on nociception in chronically stressed and control rats. We repeatedly submitted rats to restraint for 40 days. Nociception was assessed with a tail-flick apparatus. The control group presented increased tail-flick latencies after administration of CPA and dipyridamole, but this effect was not observed in the stressed group. DPCPX by itself had no effect on nociception. The analgesic effect of CPA and dipyridamole observed in the control group was reverted by DPCPX. These results indicate the involvement of adenosine A(1) receptor in the antinociception observed in control animals and suggest that the pain signaling induced by chronic stress presents a different modulation involving the adenosinergic system.
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PMID:Effect of drugs active at adenosine receptors upon chronic stress-induced hyperalgesia in rats. 1464 86

Patients with chronic pain suffer from much more affective emotional disturbance than pain sensation. The present study examined Fos expression associated with pain-related aversion in rats, using formalin-induced conditioned place avoidance (F-CPA) test, which could distinguish pain emotion from pain sensation. When pain experience was retrieved, the rats with F-CPA produced rigorous emotion-like behaviors. As a result, more Fos-LI neurons were observed in anterior cingulate cortex, retrosplenial cortex, insular cortex, parietal cortex area 2, frontal cortex area 1-3, claustrum, lateral septal area, amygdala, dorsomedial hypothalamic nucleus, central medial nucleus, paraventricular nucleus, superior colliculus, inferior colliculus and periaqueductal gray. The results for the first time mapped the brain regions associated with processing of pain affect and emotion in rats.
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PMID:Pain-related aversion and Fos expression in the central nervous system in rats. 1510 33

The pain experience includes a sensory-discriminative and an affective-emotional component. The sensory component of pain has been extensively studied, while data about the negative affective component of pain are quite limited. The anterior cingulate cortex (ACC), and amygdala are thought to be key neural substrates underlying emotional responses. Using formalin-induced conditioned place avoidance (F-CPA) and electric foot-shock conditioned place avoidance (S-CPA) models, the present study observed the effects of bilateral excitotoxic (quinolinic acid 200 nmol/microl) lesions of the ACC and amygdala on pain and fear induced negative emotion, as well as on sensory component of pain. In the place-conditioning paradigm, both intraplantar (i.pl.) injection of formalin and electric foot-shock produced conditioned place avoidance. Excitotoxin-induced lesion of either the ACC or amygdala significantly reduced the magnitude of F-CPA. However, the decrease in the magnitude of S-CPA occurred only in the amygdala, but not ACC lesioned animals. Neither ACC nor amygdala lesion significantly changed formalin-induced acute nociceptive behaviors. These results suggest that the amygdala is involved in both pain- and fear-related negative emotion, and the ACC might play a critical role in the expression of pain-related negative emotion.
Pain 2004 Jul
PMID:Contributions of the anterior cingulate cortex and amygdala to pain- and fear-conditioned place avoidance in rats. 1527 85

Using a rat formalin-induced conditioned place avoidance (F-CPA) model and Fos immunohistochemistry, the present study observed the effect of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-isoxozole propionic acid/kainite (AMPA/KA) receptors on pain-related aversion. Adult Sprague-Dawley rats were implanted with cannula in the anterior cingulate cortex (ACC) or the lateral ventricle. Before (10 min) the injection of formalin into a hindpaw on days 2 and 4 of place-conditioning trials, vehicle (0.01 M PBS), the NMDA receptors antagonist, 2-amino-5-phosphonovalerate (AP5), or the AMPA/KA receptors antagonist, 6,7-dinitroquinoxaline-2,3-dione (DNQX), was injected through the cannula. F-CPA was effectively eliminated by both intracerebroventricular (icv) and intra-ACC microinjection of AP5. In contrast, the intra-ACC or icv injection of DNQX failed to alter the conditioning scores of F-CPA compared with vehicle control group (P >0.05). Intra-ACC or icv injection of AP5 or DNQX had no effect on formalin-induced acute nociceptive behaviors. Fos immunoreactivity in the ACC was activated by retrieval of pain-related aversion, and this activation was significantly suppressed by preadministration of AP5, but not DNQX (P <0.001). These results suggest that NMDA receptors in the ACC are preferentially involved in the processing of the affective dimension of pain.
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PMID:NMDA receptors in the anterior cingulate cortex mediate pain-related aversion. 1538 Apr 91

Various studies implicate the anterior cingulate cortex (ACC) in processing pain. Combining whole-cell patch clamp recordings in rat ACC slices and a formalin-induced conditioned place avoidance (F-CPA) behavioral model, the present study was to address the effect of GABA(A) receptors on excitatory transmission to ACC layer V neurons and its possible functional significance related to pain. Removal of GABA(A) inhibition by bicuculline (10 microM) induced a novel long-lasting response in layer V neurons, which could be blocked by high divalent extracellular solution and was sensitive to relatively higher rate stimuli. Co-application of NMDA receptor antagonist APV (50 microM) and non-NMDA receptor antagonist DNQX (10 microM) completely blocked the responses. Enhancement of inhibition by intra-ACC microinjection of muscimol abolished the acquisition of F-CPA without affecting formalin-induced acute nociceptive responses. These results suggest that GABA(A) inhibition may be involved in pain-related aversion by modulating glutamate-mediated excitatory transmission in the ACC.
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PMID:GABAergic disinhibition facilitates polysynaptic excitatory transmission in rat anterior cingulate cortex. 1627 73

A-64-year-old woman, who had been treated with augmentation mammaplasty 40 years ago, came to our hospital complaining of left breast pain. The mass was ill-defined, located in the upper outer quadrant area of her breast, and was 2 cm in diameter. MRI examination showed that the tumor had a spiculation and an irregular edge. There were no regional lymph nodes in her axilla and supra-subscapular. The diagnosis was Class IV by the fine needle aspiration biopsy cytology. We diagnosed the left breast cancer being in T2N0M0, Stage IIA, then we carried out Bt (Auchincloss method) and Sentinel lymph node biopsy (SLNB). There were metastatic cancer cells in the sentinel lymph node. So, we added level II lymph nodes dissection. The histological diagnosis was papillotubular carcinoma, f+, n+ (8/11). The endocrine receptor status of the tumor was ER+, PgR+ and the HER2/neu score was 0. There was paraffinoma in the non-cancer area. We dosed 6 cycles of FEC chemotherapy (CPA 800 mg, EPI 80 mg, 5-FU 750 mg/body x 1 cycle). We recognized no side effects of the chemotherapy for the patient.
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PMID:[A case of breast cancer detected by MRI mammography after Hollywood syndrome]. 1631 41

Functional activation of NMDA receptors requires co-activation of glutamate- and glycine-binding sites. D-serine is considered to be an endogenous ligand for the glycine site of NMDA receptors. Using a combination of a rat formalin-induced conditioned place avoidance (F-CPA) behavioral model and whole-cell patch-clamp recording in rostral anterior cingulate cortex (rACC) slices, we examined the effects of d-amino acid oxidase (DAAO), an endogenous D-serine-degrading enzyme, and 7-chlorokynurenate (7Cl-KYNA), an antagonist of the glycine site of NMDA receptors, on pain-related aversion. Degradation of endogenous D-serine with DAAO, or selective blockade of the glycine site of NMDA receptors by 7Cl-KYNA, effectively inhibited NMDA-evoked currents in rACC slices. Intra-rACC injection of DAAO (0.1 U) and 7Cl-KYNA (2 and 0.2 mM, 0.6 microL per side) 20 min before F-CPA conditioning greatly attenuated F-CPA scores, but did not affect formalin-induced acute nociceptive behaviors and electric foot shock-induced conditioned place avoidance. This study reveals for the first time that endogenous D-serine plays a critical role in pain-related aversion by activating the glycine site of NMDA receptors in the rACC. Furthermore, these results extend our hypothesis that activation of NMDA receptors in the rACC is necessary for the acquisition of specific pain-related negative emotion. Thus a new and promising strategy for the prevention of chronic pain-induced emotional disturbance might be raised.
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PMID:Is endogenous D-serine in the rostral anterior cingulate cortex necessary for pain-related negative affect? 1647 80

Cizolirtine is a novel non-opioid drug which demonstrated antinociceptive activity in numerous pain models in rodents. Yet, its mechanism of action remains unknown. Several lines of evidence support the idea that adenosine (ADO) and serotonin (5-HT) modulate nociceptive signaling. Our study aimed at investigating whether these neuroactive molecules could be implicated in the mechanism of action of cizolirtine. Cizolirtine-induced antihyperalgesia was compared before and after pretreatment with ADO A(1)-A(2A) and 5-HT(1B/1D) receptor ligands in rats rendered diabetic by streptozotocin pretreatment and suffering from neuropathic pain. Cizolirtine alone (30-80 mg/kg, i.p.) significantly increased mechanical nociceptive thresholds. Acute pretreatment with the A(1)-A(2A) receptor antagonist caffeine (5 mg/kg, i.p.) or the 5-HT(1B/1D) receptor antagonist GR-127,935 (3 mg/kg, i.p.) significantly reduced the antihyperalgesic effects of cizolirtine. Conversely, cizolirtine-induced antihyperalgesia was promoted by pretreatment with either the selective A(1) receptor agonist CPA (0.3 mg/kg, i.p.) or the selective 5-HT(1B) receptor agonist CP-94,253 (3mg/kg, i.p.), and this potentiation was totally prevented by acute pretreatment with respective antagonists. Interestingly, A(1) receptor blockade by DPCPX inhibited the promoting effect of CP-94,253 on cizolirtine-induced antihyperalgesia, suggesting that the adenosine A(1)-mediated step takes place downstream the serotonin 5-HT(1B)-mediated step in the neurobiological mechanisms underlying cizolirtine action.
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PMID:Evidence for adenosine- and serotonin-mediated antihyperalgesic effects of cizolirtine in rats suffering from diabetic neuropathy. 1702 46


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