CaMK II γ down regulation protects dorsal root ganglion neurons from ropivacaine hydrochloride neurotoxicity.

T-type calcium channels are intimately involved in the local anesthetics neurotoxicity. Does CaMKIIγ regulate T-type calcium currents in local anesthetics neurotoxicity? This study generated pAd-CaMKIIγ and pAd-shRNA adenovirus vectors to up- and down-regulate CaMKIIγ mRNA expression in dorsal root ganglion neurons (DRG). Normal DRG (Normal group), empty vector DRG (Empty vector group), pAd-CaMKIIγ DRG (pAd-CaMKIIγ group) and pAd-shRNA DRG (pAd-shRNA group) were treated or untreated with 3 mM ropivacaine hydrochloride for 4 h. Cell viability, apoptosis rate, CaMKIIγ, pCaMKIIγ, Cav3.2, and Cav3.3 expression were detected. Ultrastructural changes in DRG were observed under a transmission electron microscope. The results demonstrated that the cell viability of DRG treated with ropivacaine hydrochloride decreased markedly, the apoptosis rate, CaMKIIγ, pCaMKIIγ, Cav3.2, Cav3.3 expression increased significantly. CaMKIIγ up-regulation aggravated ropivacaine hydrochloride-induced cell damage and increased Cav3.2 and Cav3.3 expression. In conclusion, CaMKIIγ regulated Cav3.2 and Cav3.3 expression in DRG, which was involved with ropivacaine hydrochloride-induced cell injury.

Spinal Transection Alters External Urethral Sphincter Activity during Spontaneous Voiding in Freely Moving Rats.

The rat is a commonly used model for the study of lower urinary tract function before and after spinal cord injury. We have previously reported that in unanesthetized freely moving rats, although phasic external urethral sphincter (EUS) activity (bursting) is most common during micturition, productive voiding can occur in the absence of bursting, which differs from results seen in anesthetized or unanesthetized restrained animals. The purpose of the present study was to characterize EUS behavior in unanesthetized, freely moving rats before and after mid-thoracic (T8) or thoraco-lumbar (T13-L1) spinal transection to determine how EUS behavior after spinal cord injury differs from that seen in anesthetized or unanesthetized restrained rats. Several abnormalities became evident that were comparable after transection at either level, including the following: repetitive non-voiding EUS contractions; increased prevalence, intensity, and duration of EUS bursting; decreased rate of urine evacuation during bursting; increased void size and decreased number of daily voids; shorter inter-burst silent period and increased frequency of bursting; and loss of the direct linear relationships that are evident in intact animals between void size and bursting silent period. These data suggest that transection-induced delayed initiation of EUS bursting allows co-contraction of the bladder and the EUS that prevents or limits urine evacuation, resulting in a detrusor-sphincter dyssynergia-like phenomenon. In addition, the higher-than-normal frequency at which EUS bursting occurs after transection is associated with shorter silent periods during which urine typically flows, which interferes with voiding by slowing the rate of urine evacuation. That results were comparable after either transection suggests that the central pattern generator responsible for EUS bursting is located caudal to the L1 spinal segment.

Intrathecal administration of Cav3.2 and Cav3.3 antisense oligonucleotide reverses tactile allodynia and thermal hyperalgesia in rats following chronic compression of dorsal root of ganglion.

AIM: The present study aimed to elucidate the role of T-subtype calcium channels (Cav3.1, Cav3.2, and Cav3.3) in the pathogenesis of neuropathic pain at spinal level. METHODS: The chronic compression of the dorsal root ganglion (CCD) rat model was adopted. The antisense oligonucleotide of Cav3.1, Cav3.2, and Cav3.3 or normal saline (NS) were intrathecally administered twice per day from the first day to the fourth day after operation. Paw mechanical withdrawal threshold and paw thermal withdrawal latency were measured to evaluate the tactile allodynia and thermal hyperalgesia, respectively. RESULTS: CCD rats developed reliable tactile allodynia and thermal hyperalgesia after operation. Intrathecal administration of antisense oligonucleotide of Cav3.2 and Cav3.3 significantly relieved tactile allodynia and thermal hyperalgesia in CCD rats, but not Cav3.1. CONCLUSION: Cav3.2 and Cav3.3 subtype calcium channels in the spinal cord may play an important role in the pathogenesis of neuropathic pain, which may contribute to the management of the neuropathic pain.