Abnormal discharge originates at the site of nerve injury in experimental constriction neuropathy (CCI) in the rat

Abstract

Rats with an experimental painful peripheral neuropathy created by placing loosely constrictive ligatures around the sciatic nerve (the CCI model) display heat-hyperalgesia on the affected limb. Pain threshold was studied using the paw withdrawal method. Electrophysiological recording from myelinated primary afferent axons revealed spontaneous impulse activity which originated at the site of nerve constriction. Overall 10.1 +/- 1.5% of the fibers sampled had spontaneous activity during the period 2-14 days post injury. The spontaneous activity fell into three patterns: (1) 'tonic' rhythmic pattern, in which the interval between successive spikes in a train was uniform, ranging from 25-50 ms (discharge rate 20-40 Hz); (2) interrupted, bursty or 'on-off' pattern, with variable silent period between high frequency bursts; and (3) 'irregular' ongoing pattern with random inter-spike intervals (5-15 Hz). There was a correlation between the prevalence and pattern of spontaneous activity, and the development of hyperalgesia post-injury. Axons trapped at the injury site including ones with and without spontaneous activity, became hyperexcitable to mechanical stimulation. The location of mechanosensitive spots progressively shifted over the period 2-14 days from the proximal to the distal part of the injury site. The spontaneous discharge of injured primary afferent fibers may contribute to abnormal sensation in these animals.

An Approach to Identify Nerve Injury-Evoked Changes that Contribute to the Development or Protect Against the Development of Sustained Neuropathic Pain

“…Peripheral nerve injury-evoked changes in impulse generation include the appearance of ectopic afferent impulses and the modification of the stimuli-evoked impulses. Following sciatic nerve injury (constriction or cutting), ectopic discharges (firing of action potentials) from the injured site (Tal and Eliav, 1996;Wall and Gutnick, 1974a;Wall and Gutnick, 1974b;Wall and Devor, 1983) and the dorsal root ganglia (Amir et al, 2002;Liu et al, 2000a;Liu et al, 1999;Liu et al, 2000b) correlate with the development of neuropathic pain. The frequency of ectopic discharges shows a transient increase within the first 24 hrs following spinal nerve ligation (Sun et al, 2005).…”

Governing role of primary afferent drive in increased excitation of spinal nociceptive neurons in a model of sciatic neuropathy

“…These can be at multiple sites along the axons, including distal terminals. Evidence from earlier studies has implicated multiple sites in the generation of ectopic activity, including peripheral nerve terminals (Albrecht et al, 2006;Kauppila et al, 2002;Pare et al, 2007), at the site of nerve injury (Bird et al, 2007;Coward et al, 2000;Devor et al, 1993;Novakovic et al, 1998;Omana-Zapata et al, 1997a,b;Tal and Eliav, 1996), along the nerve (Amir et al, 2005;Gold et al, 2003;Pertin et al, 2005), adjacent nerves (Sotgiu et al, 2006), and in the dorsal root ganglia (Amir et al, 1999;Chaplan et al, 2003;Craner et al, 2002;Liu et al, 2000bLiu et al, , 2002Michaelis et al, 2000;Na et al, 2000;Novakovic et al, 1998;Omana-Zapata et al, 1997a,b;Study and Kral, 1996;Xie et al, 1995).…”

Memory-Like Alterations inAplysiaAxons after Nerve Injury or Localized Depolarization

“…Under normal conditions, axons have not been reported to exhibit long-term, adaptive increases in excitability. However, mammalian sensory axons can display persistent hyperexcitability at sites of nerve injury (Zimmermann, 2001) and inflammation (Tal and Eliav, 1996;Eliav et al, 2001;Bove et al, 2003).…”