Refinement of symptoms of neuropathic pain measurements after various transections of the nerve endings of the sciatic and femoral nerve in rats: an exploratory behavioral analysis.

BACKGROUND: Many animal models can be used to study the underlying pathophysiological mechanisms of neuropathic pain. Most of these models rely on a partial denervation of the limb of the animal by ligating a selected nerve. In this study, we performed nerve lesions on three peripheral nerves supplying the plantar side of the rat hindpaw by differentially transecting the saphenous, the tibial, and the sural nerves alone or in paired combinations. METHODS: The development of neuropathic pain symptoms at three different anatomical areas (medial, central, and lateral) of the glabrous skin of the hindpaw was evaluated by sensory testing over a 12-wk period. Mechanical hyperalgesia (pinprick), cold allodynia (acetone), and abnormalities of hindpaw posture were continuously present in animals with tibial and tibial and saphenous nerve transection. RESULTS: Transection of the tibial and sural nerves induced cold allodynia and moderate mechanical hyperalgesia. Transection of the sural, the saphenous, or both nerves simultaneously induced no signs of specific neuropathic pain behavior and no abnormalities in posture of the affected hindpaw were noted after adequate stimulation. CONCLUSIONS: The overlapping innervation of nerve distribution can complicate the interpretation of nerve ligation studies of peripheral neuropathies.

Preparation and physicochemical characterization of biodegradable nerve guides containing the nerve growth agent sabeluzole.

The objective of this study was to develop and characterize a biodegradable drug-loaded nerve guide for peripheral nerve regeneration. Sabeluzole, a nerve growth agent, was selected as model compound. Four biodegradable polymers were selected for this study: a copolymer of polylactic acid and polycaprolactone (PCL); a copolymer of polyglycolic acid and polycaprolactone PCL; a copolymer of PCL/polydioxanone (PDO) and PDO. Placebo and drug loaded nerve guides were obtained by melt compression and melt extrusion. It was observed that melt compression and melt extrusion are feasible techniques to prepare the nerve guides. Based on the physicochemical characterization, all samples show absence of crystalline sabeluzole, indicating the formation of an amorphous dispersion. The in vitro release measurements show that the release of sabeluzole is complete, reproducible and can be controlled by the proper selection of the polymer. The release mechanism for all samples follows Fickian release behaviour.

A modeling approach to the analysis of nerve regenerative experiments.

Many experiments aiming at the investigation of nerve repair involve elaborate testing over a certain time period. Data arising from such experiments are often analyzed by time-point. Such a cross-sectional approach is often very inefficient. In this paper, we consider a case study in which repeated measurements of two response variables assumed to be Poisson distributed are obtained. We show how a repeated measures modeling approach, based on generalized linear models, can handle both responses in one model and improve the inference in the nerve repair experiments. The benefits of the model as well as problems that can occur are illustrated and discussed.