Introduction: Pain is a complex phenomenon and in many diseases is the cardinal manifestation. In many of them, the source of pain is obscure and in turn curing pain also becomes difficult. Finding a new regulatory me...Introduction: Pain is a complex phenomenon and in many diseases is the cardinal manifestation. In many of them, the source of pain is obscure and in turn curing pain also becomes difficult. Finding a new regulatory mechanism for pain perception and processing such as alternation of neurogenesis may establish a new treatment. Methods and Materials: In this study, 32 male Sprague-Dawley rats were randomly divided into four groups: social, isolated, morphine-treated socialized (MTS) and morphine-treated isolated (MTI). After injection of BrdU for 14 days (50 mg/kg/rat/day/i.p) and morphine for seven days from day 8 (3 mg/kg/rat/day/i.p), rats were performed tail flick test and then sacrificed. Brains were prepared for assessing neurogenesis and serums were collected for assessing glutathione. Results: In tail flick test isolated and morphine-treated isolated rats had decreased sensitivity to pain stimuli compared to social and morphine-treated socialized rats, respectively. In assessing neurogenesis, isolated and morphine-treated isolated rats had reduced numbers of newly generated neurons compared to social and morphine-treated socialized rats, respectively. Glutathione in serum in isolated and morphine-treated isolated rats increased compared to social and morphine-treated socialized rats, respectively. Conclusion: Reduction of neurogenesis was associated with reduced pain sensitivity in isolated groups. So, isolation may alleviate pain and reduce pain threshold and sensitivity.展开更多
Pain is a sensation related to potential or actual damage in some tissue of the body. The mainstay of medical pain therapy remains drugs that have been around for decades, like non-steroidal anti-inflammatory drugs (...Pain is a sensation related to potential or actual damage in some tissue of the body. The mainstay of medical pain therapy remains drugs that have been around for decades, like non-steroidal anti-inflammatory drugs (NSAIDs), or opiates. However, adverse effects of opiates, particularly tolerance, limit their clinical use. Several lines of investigations have shown that systemic (intraperitoneal) administration of NSAIDs induces antinociception with some effects of tolerance. In this review, we report that repeated microinjection of NSAIDs analgin, clodifen, ketorolac and xefocam into the central nucleus of amygdala, the midbrain periaqueductal grey matter and nucleus raphe magnus in the following 4 days result in progressively less antinociception compared to the saline control testing in the tail-flick reflex and hot plate latency tests. Hence, tolerance develops to these drugs and cross-tolerance to morphine in male rats. These findings strongly support the suggestion of endogenous opioid involvement in NSAIDs antinociception and tolerance in the descending pain-control system. Moreover, the periaqueductal grey-rostral ventro-medial part of medulla circuit should be viewed as a pain-modulation system. These data are important for human medicine. In particular, cross-tolerance between non-opioid and opioid analgesics should be important in the clinical setting.展开更多
文摘Introduction: Pain is a complex phenomenon and in many diseases is the cardinal manifestation. In many of them, the source of pain is obscure and in turn curing pain also becomes difficult. Finding a new regulatory mechanism for pain perception and processing such as alternation of neurogenesis may establish a new treatment. Methods and Materials: In this study, 32 male Sprague-Dawley rats were randomly divided into four groups: social, isolated, morphine-treated socialized (MTS) and morphine-treated isolated (MTI). After injection of BrdU for 14 days (50 mg/kg/rat/day/i.p) and morphine for seven days from day 8 (3 mg/kg/rat/day/i.p), rats were performed tail flick test and then sacrificed. Brains were prepared for assessing neurogenesis and serums were collected for assessing glutathione. Results: In tail flick test isolated and morphine-treated isolated rats had decreased sensitivity to pain stimuli compared to social and morphine-treated socialized rats, respectively. In assessing neurogenesis, isolated and morphine-treated isolated rats had reduced numbers of newly generated neurons compared to social and morphine-treated socialized rats, respectively. Glutathione in serum in isolated and morphine-treated isolated rats increased compared to social and morphine-treated socialized rats, respectively. Conclusion: Reduction of neurogenesis was associated with reduced pain sensitivity in isolated groups. So, isolation may alleviate pain and reduce pain threshold and sensitivity.
基金supported by the grant from Georgian National Science Foundation,No.GNSF/ST07/6-234
文摘Pain is a sensation related to potential or actual damage in some tissue of the body. The mainstay of medical pain therapy remains drugs that have been around for decades, like non-steroidal anti-inflammatory drugs (NSAIDs), or opiates. However, adverse effects of opiates, particularly tolerance, limit their clinical use. Several lines of investigations have shown that systemic (intraperitoneal) administration of NSAIDs induces antinociception with some effects of tolerance. In this review, we report that repeated microinjection of NSAIDs analgin, clodifen, ketorolac and xefocam into the central nucleus of amygdala, the midbrain periaqueductal grey matter and nucleus raphe magnus in the following 4 days result in progressively less antinociception compared to the saline control testing in the tail-flick reflex and hot plate latency tests. Hence, tolerance develops to these drugs and cross-tolerance to morphine in male rats. These findings strongly support the suggestion of endogenous opioid involvement in NSAIDs antinociception and tolerance in the descending pain-control system. Moreover, the periaqueductal grey-rostral ventro-medial part of medulla circuit should be viewed as a pain-modulation system. These data are important for human medicine. In particular, cross-tolerance between non-opioid and opioid analgesics should be important in the clinical setting.