Spinal cord stimulation in animal models of mononeuropathy: effects on the withdrawal response and the flexor reflex

Abstract

Spinal cord stimulation (SCS) is efficacious for pain due to injury of peripheral nerves, and therefore models of mononeuropathy appear to be particularly suitable for an experimental approach to the study of mechanisms underlying the clinical effect of this mode of treatment in chronic neuropathic pain. Virtually all previous experimental studies on SCS have utilized acute and nociceptive types of peripheral pain stimuli to explore the attenuating effects of SCS. In the present study we made use of the two models of supposedly painful neuropathy developed by Bennett and Xie (1988) and Seltzer et al. (1990) to explore the effect of SCS applied with stimulus parameters similar to those used in clinical practice. In rats subjected to ligatures of the sciatic nerve according to these two methods, SCS was applied via chronically implanted electrodes, or acutely via a laminectomy in the lower thoracic region. In awake, freely moving animals SCS produced a marked increase of the withdrawal thresholds to innocuous mechanical stimuli in the form of von Frey filaments. This threshold elevation lasted for up to 40 min after 10 min of SCS. In about one-half of the animals there was also a moderate, but short-lasting increase in the intact leg. The degree and duration of the withdrawal threshold elevation was clearly related to the intensity of SCS which was kept below the level of which a response in the thoracic or leg musculature was produced. In a second series of experiments the effect of SCS, applied acutely via a laminectomy, on the early component (latency: 8-12 msec) of the flexor reflex was studied. As a result of nerve ligation with either of the methods used, the thresholds for evoking the early as well as the late component in the nerve-ligated leg were significantly lower than in the intact one. SCS resulted in a marked and long-lasting increase of the threshold of the early component in the nerve-ligated leg. On the intact side only a slight and short-lasting increase was observed. The late, C fibre-mediated component was not influenced by SCS. The first component of the flexor reflex is conceivably mediated by A beta-fibre activation and it presumably corresponds to the withdrawal response induced by innocuous mechanical stimuli. The lack of effect of SCS on the late reflex component indicates that it selectively influences transmission of A-fibre activity. (ABSTRACT TRUNCATED AT 400 WORDS)

Mode of Action of Spinal Cord Stimulation in Neuropathic Pain

“…This notion is further supported by the finding that the threshold of the early component of the flexor reflex, which is Ab-fiber mediated, is elevated whereas the late C-fiber-dependent phase was found to be unaffected. 22 However, it has also been reported that the C-fiber flexor reflex can be significantly attenuated, but this observation was made in normal, intact animals. 23 Recently, the effect of SCS on long-term potentiation (LTP) has been investigated.…”

Ensheathing glia transplants promote dorsal root regeneration and spinal reflex restitution after multiple lumbar rhizotomy

“…The maximal amplitude (baseline to peak) and latency to onset of the evoked MUAPs were measured for the first and second components of the response. 26 The first component appears after low-intensity stimuli that excite ␤-amyloid (A␤) afferent fibers as a short-lasting biphasic or triphasic deflection, whereas the second component is elicited by excitation of A␦ afferent fibers at higher stimulus intensity and consists in a longer-lasting volley of MUAPs.…”

Mechanisms of Spinal Cord Stimulation in Neuropathic Pain

“…Spinal cord stimulation induced an increase of these abnormally lowered withdrawal thresholds, which are mediated through alpha and beta fibers. These observations suggests SCS predominantly affects pain related to abnormal A fiber function, as in allodynia ( Handwerker et al, 1975;Carstens & Campbell, 1988;Garcia-Larrea et al, 1989;Meyerson et al, 1995;Oakley & Prager, 2002). Repetitive noxious stimulation of primary afferent fibers after peripheral nerve injury induces long-term changes of the excitability of spinal cord neurons (Rygh et al, 1999).…”