Temporal progression and extent of the return of sensation in the foot provided by the saphenous nerve after sciatic nerve transection and repair in the rat - Implications for nociceptive assessments

Chair of General Pathology & Neuropathology, Institute of Veterinary Pathology, Ludwig-Maximilians University, Munich, Germany.
Somatosensory and Motor Research (Impact Factor: 0.64). 03/2007; 24(1-2):1-13. DOI: 10.1080/08990220601116329
Source: PubMed


Sensory testing, by providing stimuli for nociceptors of the foot, is a popular method of evaluating sensory regeneration after damage to the sciatic nerve in the rat. In the following study, 20 rats were submitted to double transection of the sciatic nerve. The subsequent 14 mm gap was repaired through guidance interponation. In order to evaluate nerve regeneration, sensory testing was performed additionally to other methods, which included motor testing, morphometry, and electron microscopic assessments of nerves. Somatosensory testing revealed that all animals exhibited next to the same amount of sensory reinnervation on their foot regardless of their experimental group. In motor tests, however, two out of the three experimental groups did not improve at all. These groups also failed to show neural regrowth in morphometric and electron microscopic assessments of the associated nerve. Retrograde tracing was able to prove the saphenous nerve as an alternative source of sensory reinnervation in animals with failed sciatic regeneration. This means that results of sensory testing in the rat should be treated with caution, taking into account the areas tested and the likelihood that in these areas saphenous sprouting could have taken place. Furthermore, it is strongly advised that somatosensory testing should be conducted only on toe 5.

8 Reads
    • "Such motor dependency can be circumvented if the response to the stimulus can be elicited from an area of the body which was unaffected by the nerve injury (Nichols et al., 2005) Animals display a hypersensitive withdrawal response following nerve injuries that is associated with sensitization of cutaneous nociceptors to mechanical and thermal stimuli. An important consideration for the validity of these behavioural tests is to ensure that evaluation is done in areas of the foot that are definitely not affected by sprouting of neighbouring intact nerves, taking into account the territories of innervation of the sciatic and saphenous nerves in the hindpaw (Fig. 4C), and of median and ulnar nerves in the forepaw (Rupp et al., 2007; Cobianchi et al., 2014). On the other hand, selective stimulation applied to specific sites in the paw allow assessment in parallel of nerve regeneration and collateral sprouting effects on pain and reinnervation. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Peripheral nerve injuries usually lead to severe loss of motor, sensory and autonomic functions in the patients. Due to the complex requirements for adequate axonal regeneration, functional recovery is often poorly achieved. Experimental models are useful to investigate the mechanisms related to axonal regeneration and tissue reinnervation, and to test new therapeutical strategies to improve functional recovery. Therefore, objective and reliable evaluation methods should be applied for the assessment of regeneration and function restitution after nerve injury in animal models. This review gives an overview of the most useful methods to assess nerve regeneration, target reinnervation and recovery of complex sensory and motor functions, their values and limitations. The selection of methods has to be adequate to the main objective of the research study, either enhancement of axonal regeneration, improving regeneration and reinnervation of target organs by different types of nerve fibers, or increasing recovery of complex sensory and motor functions. It is generally recommended to use more than one functional method for each purpose, and to perform also morphological studies of the injured nerve and the reinnervated targets. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    European Journal of Neuroscience 07/2015; DOI:10.1111/ejn.13033 · 3.18 Impact Factor
    • "Rats display a characteristic hypersensitive withdrawal response following sciatic nerve transection that is associated with a differential sensitization of cutaneous nociceptors to mechanical and thermal stimuli: myelinated nociceptors have significantly lower mechanical and thermal thresholds whereas polymodal unmyelinated C fibers display lower thresholds in response to heat only (Markus et al., 1984; Jankowski et al., 2009; Kemp et al., 2011). Another important consideration for the validity of the behavioral tests is to ensure that somatosensory evaluation is done in areas of the foot that are definitely not affected by sprouting of the saphenous nerve, namely in toe 5 (Rupp et al., 2007). The saphenous nerve branch of the femoral nerve, remaining intact after section of the sciatic nerve (and the sural nerve), sprouts to innervate denervated sensory nerve territories within days (Devor and Govrin-Lippmann, 1979). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Animal models of nerve compression, crush, and transection injuries of peripheral nerves have been subject to extensive study in order to understand the mechanisms of injury and axon regeneration and to investigate methods to promote axon regeneration and improve functional outcomes following nerve injury. Six outcome measures of regenerative success including axon and neuron counts, muscle and motor unit contractile forces, and behavior are reviewed in the context of nerve injury types, crush, transection and nerve repair by direct coaptation, or transection and repair via a nerve graft or conduit. The measures are evaluated for sciatic, tibial, common peroneal, femoral, single nerve branches such as the soleus nerve, and facial nerves. Their validity is discussed in the context of study objectives and the nerve branch. The case is made that outcome measures of axon counts and muscle contractile forces may be valid during the early phases of axon regeneration when regenerating sprouts emerge asynchronously from the proximal nerve stump and regenerate towards their denervated targets. However, care must be taken especially when experimental interventions differentially affect how many neurons regenerate axons and the number of axons per neuron that sprout from the proximal nerve stumps. Examples of erroneous conclusions are given to illustrate the need for researchers to ensure that the appropriate outcome measures are used in the evaluation of the success of peripheral nerve regeneration.
    Annals of anatomy = Anatomischer Anzeiger: official organ of the Anatomische Gesellschaft 05/2011; 193(4):321-33. DOI:10.1016/j.aanat.2011.04.008 · 1.48 Impact Factor
  • Source
    • "The surgical approach for exposing the sciatic nerve, the length and location of the segment excised from the sciatic nerve, the type and location of closing-up sutures, anaesthesia and perioperative management were identical to those applied in the previous study (Rupp et al., 2007b). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Striking inconsistencies between the results of morphometric and electrophysiologic examinations of the regenerating nerve were observed in a previous study featuring the bridging of a 14 mm gap in the rat sciatic nerve. To shed light on this dichotomy, seven further rats were subjected to permanent sciatic nerve transection and assessed electrophysiologically, histologically and by retrograde axonal tracing at various postoperative intervals (1 h to 8 weeks). The results of the histological examinations and retrograde tracing revealed that in spite of the fact that compound muscle action potentials could be recorded in the gastrocnemius muscle, no reinnervation of the gastrocnemius muscle, either physiological or aberrant, had actually taken place. Furthermore, it was established that the electrical activity recorded in the gastrocnemius muscle after stimulation of the proximal or distal stump is generated by surrounding hind limb muscles unaffected by denervation. These are stimulated either directly, or indirectly due to spreading of the impulse. It is therefore strongly recommended that caution should be exercised when interpreting recordings from the gastrocnemius muscle after stimulation of a regenerating sciatic nerve in laboratory rodents.
    Journal of Neuroscience Methods 12/2007; 166(2):266-77. DOI:10.1016/j.jneumeth.2007.07.015 · 2.05 Impact Factor
Show more