We discovered a variation of rat sciatic nerve anatomy as an incidental finding during the anatomical exploration of the nerve lesion site in a rat neuropathic pain model. To confirm the composition and distribution of rat sciatic nerve, macroscopic anatomical investigation was performed in both left and right sides in 24 adult Sprague-Dawley rats. In all rats, the L4 and L5 spinal nerves were fused tightly to form the sciatic nerve. However, the L6 spinal nerve did not fuse with this nerve completely as a part of the sciatic nerve, but rather sent a thin branch to it in 13 rats (54%), whereas in the remaining 11 rats (46%), L6 ran separately along with the sciatic nerve. Also, the L3 spinal nerve sent a thin branch to the L4 spinal nerve or sciatic nerve in 6 rats (25%). We conclude that the components of sciatic nerve in Sprague-Dawley rats vary from L3 to L6; however, the major components are L4 and L5 macroscopically. This finding is in contrast to the standard textbooks of rat anatomy which describe the sciatic nerve as having major contributions from L4, L5, and L6.

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Chronic intrathecal catheters were variously located in the rat spinal subarachnoid space in the transverse plane, and lateral subarachnoid placement of the catheter (58%) was frequently observed, whereas dorsal subarachnoid placement occurred in 33%.

Aims The clinical relevance of adding the acetylcholinesterase inhibitor donepezil to existing gabapentin treatment in patients with post-traumatic neuropathic pain was explored in this open-label study. The two drugs have previously shown synergism following co-administration in nerve-injured rats [1,2]. Methods The study comprised two consecutive periods of minimum six weeks: (1) titration of gabapentin until highest tolerable dose or maximum 24GG mg daily; and (2) addition of donepezil 5 mg once daily to the fixed gabapentin dose. Efficacy and tolerability were assessed by ratings of pain intensity, questionnaires for pain and health-related quality of life, and reporting of adverse events and analgesic rescue medication. Pain scores were also analyzed using mixed-effects analysis (i.e. incorporating inter-subject variability) with the software NONMEM. Results Eight patients commenced treatment with donepezil upon the gabapentin titration period, of which two withdrew due to adverse events. Addition of donepezil reduced pain by >35% in four of six patients compared to gabapentin monotherapy. Mixed-effects analysis revealed that pain scores were significantly lower during co-administration (p < 0.05 combination vs. monotherapy). Donepezil was well tolerated in combination with gabapentin. At the end of study, three patients wished to continue combination therapy with gabapentin and donepezil. Conclusions Donepezil may provide additional analgesia to neuropathic pain patients with insufficient pain relief from gabapentin as monotherapy. Further confirmation in controlled clinical trials is justified. Mixed-effects analysis was sensitive enough to detect statistically significant effects, showing its usefulness in small-scale trials and/or when data is associated with high variability.

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