Serotonergic signaling inhibits hyperalgesia induced by spinal cord damage

Horiuchi, Hideki; Ogata, Tadanori; Morino, Tadao; Takeba, Jun; Yamamoto, Haruyasu

doi:10.1016/s0006-8993(02)04055-6

Cited by 30 publications

(27 citation statements)

References 36 publications

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“…We thought that gender difference may affect the mortality of the animals, and that female rats would be suitable for evaluation of sensory abnormality after SCI. When we observed the threshold against heat stimulation in normal and the sham animals, no changes in threshold was observed within 7 days, 5 suggesting that estrous cycle did not affect pain sensation in this study. Therefore, we used female rats in this experiment.…”

Section: Animalsmentioning

confidence: 53%

“…Significant hyperalgesia was observed in SCI animals from the second to the fifth day after compression. 5 The withdrawal latency returned to normal on the following day after the compression procedure. The reason why longer compression periods did not produce hypersensitivity against thermal stimulation is still unclear.…”

Section: Discussionmentioning

confidence: 91%

“…We previously established a model for rat hyperalgesia after spinal cord compression injury. 5 Our method aims to model ischemia-induced hyperalgesia. When a 20-gweight is slowly placed on the thoracic spinal cord, almost complete ischemia can be achieved by minimum force.…”

Section: Discussionmentioning

confidence: 99%

“…The pain sensations are believed to be controlled by a balance between excitatory and inhibitory signals. The typical stimulatory signaling molecules are glutamate 2,3 and substance P, 4 and the inhibitory signaling molecules are serotonin, 5 noradrenaline 6 and GABA (g-amino-butyric acid). 7 Adenosine, an endogenous neuromodulator, controls neuronal membrane potential through adenosine receptors.…”

Section: Introductionmentioning

confidence: 99%

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Adenosine A1 receptor agonists reduce hyperalgesia after spinal cord injury in rats

et al. 2010

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Study design: An in vivo study using a spinal cord compression model in rats. Objectives: To evaluate the effect of adenosine on thermal hyperalgesia after spinal cord injury (SCI). Summary of background data: After SCI, some patients suffer dysesthesia that is unresponsive to conventional treatments. We previously established a rat thoracic spinal cord mild-compression model by which we were able to induce thermal hyperalgesia in the hind limbs. Methods: The thoracic spinal cord was compressed gently using a 20-g weight for 20 min. The withdrawal latency in response to thermal stimulation was monitored bilaterally in the hind limbs using Hargreaves' Plantar test apparatus. Results: SCI-induced thermal hyperalgesia was mimicked by the intrathecal application of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a selective adenosine A1 receptor antagonist. Hyperalgesia induced by SCI was significantly inhibited by the intrathecal application of 10-30 nmol chloro-adenosine (Cl-adenosine), a nonselective adenosine receptor agonist. The effect of Cl-adenosine (10 nmol) on hyperalgesia after SCI was blocked by the simultaneous application of DPCPX. Intrathecal application of R(À)N6-(2phenylisopropyl) adenosine (R-PIA; 10 nmol), a selective A1 receptor agonist, also inhibited SCI-induced hyperalgesia. In contrast, intrathecal application of CGS21680, a selective adenosine A2a receptor agonist, did not inhibit SCI-induced hyperalgesia. Conclusions: These results suggest that adenosine inhibits hyperalgesia through the stimulation of A1 receptors. Adenosine or adenosine A1 receptor agonists should be considered as candidates for new therapeutic methods for treating post-SCI dysesthesia.

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Section: Animalsmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Adenosine A1 receptor agonists reduce hyperalgesia after spinal cord injury in rats

et al. 2010

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“…In the case of 5-hydroxytryptamine (5-HT), serotonin neurons originate from the raphe nucleus where CCK-AR is located, and project to the whole brain, including the hippocampus and hypothalamus (23). Based on this information, we measured monoamine contents after completion of the plantar test in OLETF and LETO rats as well as CCK-AR(−/ −) and wild-type mice.…”

Section: Introductionmentioning

confidence: 99%

Disturbance of Response to Acute Thermal Pain in Naturally Occurring Cholecystokinin-A Receptor Gene Knockout Otsuka Long-Evans Tokushima Fatty (OLETF) Rats

et al. 2006

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Abstract. Otsuka Long-Evans Tokushima Fatty (OLETF) rats lack cholecystokinin-A receptor (CCK-AR) because of a genetic abnormality. We observed that body temperature homeostasis in response to changes in ambient temperature was deteriorated in OLETF rats, while the functions of the signal outputs from the hypothalamus to effectors were not impaired. Deteriorated homeostasis was also seen in CCK-AR deficient (−/ −) mice. In the present study, we examined whether the sensory pathway involved in transmitting signals about temperature from the skin to the brain was impaired in OLETF rats. To elucidate the involvement of CCK-AR function, we conducted the same experiment in CCK-AR(−/ −) mice. Responses to thermal pain were assessed using the Hargreaves' plantar test apparatus. Shortening of withdrawal latency was observed in OLETF rats compared to control rats, indicating thermal hyperalgesia. Behavioral responses following paw withdrawal were disturbed in OLETF rats. The 5-hydroxytryptamine (5-HT) and 5-hydroxyindole acetic acid contents in the hippocampus and frontal cortex of OLETF rats were significantly higher than in those of the controls. CCK-AR(−/ −) mice did not show any differences from wild-type mice. In conclusion, OLETF rats showed thermal hyperalgesia and disturbed responses to thermal pain, and an alteration of 5-HT function might have a role in this disturbance.

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Blockade of the 5‐HT₃ receptor for days causes sustained relief from mechanical allodynia following spinal cord injury

Chen¹,

Oatway²,

Weaver³

2008

J of Neuroscience Research

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Chronic neuropathic pain is a frequent, serious outcome of spinal cord injury (SCI) that is highly refractory to treatment. Serotonin can contribute to neuropathic pain after SCI, as suggested by our previous observation that transient blockade of the 5-HT(3) receptor by intrathecal injections of the antagonist ondansetron reduces mechanical allodynia after SCI in rats. The current study determined whether intrathecal or intravenous infusion of ondansetron for 3 or 7 days, respectively, could cause sustained blockade of mechanical allodynia at and below the level of a twelfth thoracic clip compression injury in rats. Intrathecal 3-day infusion of ondansetron (2.0 microg/hr), targeted to the cord rostral to the SCI and commencing at 28 days after SCI, decreased at-level mechanical allodynia by 40% and below-level allodynia by 60% compared with saline-treated rats (controls). This reduction was sustained throughout drug delivery and for 1 day afterward. During the next 3 days, allodynia gradually returned toward the values of saline-treated rats. An initial experiment showed that bolus intravenous injections of ondansetron (20-100 microg) at 28 days after SCI decreased both at- and below-level allodynia for 90-120 min. Intravenous 7-day infusions (20 microg/hr), commencing at 28 days after SCI, significantly decreased at-level allodynia by 48% and below-level allodynia by 51% compared with controls. This reduction of allodynia lasted throughout the infusion and for 1-3 days afterward while pain responses gradually approached those of controls. These findings suggest a potential role of 5-HT(3) receptor antagonism in the relief of neuropathic pain after SCI in humans.

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Serotonergic signaling inhibits hyperalgesia induced by spinal cord damage

Cited by 30 publications

References 36 publications

Adenosine A1 receptor agonists reduce hyperalgesia after spinal cord injury in rats

Adenosine A1 receptor agonists reduce hyperalgesia after spinal cord injury in rats

Disturbance of Response to Acute Thermal Pain in Naturally Occurring Cholecystokinin-A Receptor Gene Knockout Otsuka Long-Evans Tokushima Fatty (OLETF) Rats

Blockade of the 5‐HT₃ receptor for days causes sustained relief from mechanical allodynia following spinal cord injury

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Serotonergic signaling inhibits hyperalgesia induced by spinal cord damage

Cited by 30 publications

References 36 publications

Adenosine A1 receptor agonists reduce hyperalgesia after spinal cord injury in rats

Adenosine A1 receptor agonists reduce hyperalgesia after spinal cord injury in rats

Disturbance of Response to Acute Thermal Pain in Naturally Occurring Cholecystokinin-A Receptor Gene Knockout Otsuka Long-Evans Tokushima Fatty (OLETF) Rats

Blockade of the 5‐HT3 receptor for days causes sustained relief from mechanical allodynia following spinal cord injury

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Blockade of the 5‐HT₃ receptor for days causes sustained relief from mechanical allodynia following spinal cord injury