Whereas in some experiments only a single peak of osteoclast formation was observed, in other experiments several waves of osteoclast formation and death were evident

e considerations led us to thoroughly characterize the homogeneous model of complete transection of the spinal cord at thoracic level with regard to its possible relevance for studying central neuropathic pain, associated neuroplasticity changes and responses to drugs used to alleviate pain in SCI patients. Spinal Cord Transection-Induced Allodynia in Rats Clinical State of Spinal Cord Transected Rats Despite complete transection of the spinal cord, rats showed a relatively good physiological state. The lack of micturition reflex and the hematuria, which are commonly encountered in paraplegic patients, usually resolved within 9 days postsurgery. Otherwise, their fur was clean, and very probably because they shared their cage with a congener, autotomia never occurred. Although rats lose weight for the first week after surgery, as a consequence of hindlimb muscles atrophy, they subsequently gained weight at the same rate as sham-operated rats, as expected from animals in 12695532 good health. Effects of Spinal Cord Transection on Hindlimb Sensitivity Just after the lesion, hindlimbs no longer responded by a reflex motor reaction to cutaneous mechanical stimulation at high intensity. Motor reaction then reappeared progressively up to a level corresponding to that found in control animals around the second week postsurgery. A marked hyper-reflexivity subsequently developed, along with spasticity, which reached their maximum approximately 7 weeks post-surgery and were still fully present on the last day of our study. Marked alterations of motor reflexes also occur in humans with complete spinal cord transection, as evidenced by the exacerbated response in the H reflex of hindlimb muscles. Such facilitated reflex responses may be due to a-motoneurons hyperexcitability. Indeed, spinal cord transection causes an up-regulation of constitutively active 5-HT2C receptors expressed by motoneurons, and the reinforcement of their membrane depolarizing influence has been demonstrated to contribute to motoneuron hyperexcitability in lesioned rats. On the other hand, spasticity could also be accounted for by a down regulation of the potassium-chloride cotransporter KCC2 within the lumbar spinal cord below transection. Although spasticity can be painful in humans, and below-level pain exists in patients with extensive spinal cord injury, hyper-reflexivity and spasticity at hindlimb level could not be related to pain behavior in SCT rats because completeness of the lesion prevented the nociceptive messages to reach the sensory cortex where they can generate pain sensation. Along with mechanical hypersensitivity, SCT rats also developed heat and cold hypersensitivity as 15863272 shown by the reduced latency of hindpaw withdrawal after immersion in water at 46uC or 10uC. Heat hypersensitivity has already been described in mice after spinal cord contusion and transection, and cold hypersensitivity at hindpaw level has been well documented in rats with contused spinal cord. Whether or not similar neuroplasticity mechanisms underlay thermal and mechanical hypersensitivity at hindpaw level in SCT rats is a pending question to be addressed in future studies. In particular, because thermal hypersensitivity was evidenced from a motor response, IL-1b, TNF-a and IL-10 in dorsal root ganglia and spinal purchase IPI-145 tissues in spinal cord-transected rats. Real-time RT-qPCR determinations were made in T6T8 and T9T11 dorsal root ganglia and T6T8 and T9T11 spinal segments at day 2, 15 or 60 after spina

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