Antiallodynic effects of intrathecal tianeptine in a neuropathic pain rat

BACKGROUND: Tianeptine is an antidepressant drug which is used for treating depression. Interestingly, the tianeptine has shown antinociceptive effects within a variety of nociceptions. The aim of this study is to investigate the antiallodynic effects of tianeptine in neuropathic pain rats and also determine the involvements of serotonergic, alpha-2 adrenergic and adenosine receptors at the spinal level. METHODS: Neuropathic pain was induced by ligation of left lumbar at 5th and 6th spinal nerves in male Sprague-Dawley rats. PE-10 catheters were placed into the thoracolumbar subarachnoid space for drug injections. Mechanical allodynia was evaluated by measuring the withdrawal threshold to von Frey filament when applying on the plantar surface of rats. The effects of intrathecal tianeptine were observed at 15, 30, 60, 90, 120, 150, 180 minutes after delivery. Antagonists for serotonergic (dihydroergocristine), alpha-2 adrenergic (yohimbine) and adenosine (CGS 15943) receptors were intrathecally administered 10 minutes prior to tianeptine in order to evaluate the involvement of both receptors. RESULTS: Intrathecal tianeptine increased dose-dependently at the withdrawal threshold in the ligated paw. Pretreatment with intrathecal dihydroergocristine, yohimbine and CGS 15943 antagonized the antiallodynic effects of tianeptine. CONCLUSIONS: These results suggested that intrathecal tianeptine attenuates the spinal nerve ligation induced tactile allodynia. Serotonergic, alpha-2 adrenergic and adenosine receptors are all involved in the antiallodynic effects of tianeptine at the spinal level.

The effect of inducing morphine tolerance on anti-allodynic action of gabapentin in spinal nerve-ligated rat / 대한마취과학회지

BACKGROUND: Morphine is more effective in inflammatory or acute pain than neuropathic pain. Recently, some reports demonstrated that the development and maintenance of opioid tolerance and neuropathic pain have similar aspects. Here, we evaluated whether morphine tolerance affects the anti-allodynic effect of gabapentin in spinal-nerve ligated rat. METHODS: Male Sprague-Dawley rats weighing 100-120 g received L5,6 spinal nerve ligation to induce neuropathic pain. Rats showing allodynia were implanted with intrathecal (i.t.) catheter to administer the experimental drugs into the subarachnoid space. To induce olerance to morphine, 15 microgram of morphine was injected via i.t. catheter twice a day for 7 days, and the effect of i.t. gabapentin on the paw withdrawal threshold was examined using the von Frey test before and after the development of morphine tolerance. RESULTS: Ligation of spinal nerves decreased the paw withdrawal threshold. Intrathecal morphine initially increased the paw withdrawal threshold, but this effect decreased gradually over time. However, morphine tolerance did not influence the effect of gabapentin on withdrawal threshold. CONCLUSIONS: Morphine tolerance did not affect gabapentin efficacay in a neuropathic pain model.

The Mechanical Antiallodynic Effect of Intrathecal Lamotrigine in Rats with Spinal Nerve Ligation / 대한통증학회지

BACKGROUND: A nerve ligation injury may produce a tactile allodynia. The effects of intrathecally delivered lamotrigine on allodynia induced due to fifth and sixth lumbar spinal nerves ligation in rats, using lumbar intrathecal catheters were examined. METHODS: Sprague-Dawley rats (body weight 160-180 g) were prepared by tightly ligating the fifth and sixth left lumbar spinal nerves, with the implantation of a chronic intrathecal catheter for drug administration. Mechanical allodynia and allodynic threshold were measured using von Frey filaments and the updown method, respectively. After the baseline hind paw withdrawal thresholds had been obtained, lamotrigine (10, 30, 100 and 300microgram) was administered intrathecally. Thereafter, the dose-response curves and 50% effective dose (ED50) were obtained. Motor dysfunction was assessed by observing the righting/stepping reflex responses and abnormal weight bearing. RESULTS: Intrathecal administration of lamotrigine produced a dose-dependent antiallodynic action (ED50 = 61.7microgram). Mild motor weakness was observed with 300microgram lamotrigine, but no severe motor impairment was found. CONCLUSIONS: It is suggested that intrathecal lamotrigine could produce moderate antagonism of mechanical allodynia at the spinal level in a rat neuropathic pain model with minimal motor weakness.