Characteristics of A- and C-fibers ending in a sensory nerve neuroma in the rat

Abstract

1. We have studied, in vivo, the degree of spontaneous activity, responsiveness to mechanical and chemical stimuli, and the conduction velocities in C- and A-fibers ending in the neuromas formed 8-66 days after ligation and transection of a cutaneous sensory nerve in the rat. 2. Some of these C- and A-fibers developed ongoing activity. The percentage varied considerably between neuromas in different animals, from 0 to 23% (mean, 4.2%), with no major variation in the incidence as a function of neuroma age. 3. The endings of the fibers in the neuroma could be excited by both mechanical and chemical stimuli. From 0 to 26% (mean, 13%) of these fibers had mechanosensitive endings, some of which were located in the muscle/facia tissue outside the neuroma itself. Some fibers were excited by direct application of chemicals to their endings in the neuroma; 3.0% of A- and C-fibers responded to bradykinin, 2.0% to histamine, and 2.8% to adrenaline. There was no systemic variation in the percentages of mechano- or chemosensitive fibers with neuroma age. 4. The C-fiber action potentials showed a continuing decrease in conduction velocities over the 9 wk after nerve transection. More than 4 wk after transection, the conduction velocity of neuroma fibers was 88% that of C-fibers of normal saphenous nerve. 5. We conclude that fibers in a cutaneous nerve neuroma have some sensory capabilities similar to those in normal nerves terminating in the skin. This could be because they are retained after the nerve is transected or because they are initially lost but then regenerate. However, the numbers are restricted, probably because the fibers remain isolated from factors produced by their target skin tissue that are necessary for development and maintenance of sensory functions.

Comparison of three rodent neuropathic pain models

“…It is well known that ectopic discharges are produced by injured nerve fibers and their dorsal root ganglion (DRG) cells (Wall and Gutnick 1974;Devor and Janig 1981;Korenman and Devor 1981 ;Scadding 1981;Blumberg and J[inig 1984;H~ibler et al 1987;Welk et al 1990;Devor et al 1994). These ectopic discharges then enter the spinal cord and sensitize spinal dorsal horn neurons, since a sustained input caused by electrical stimulation of C fibers at "wind-up" frequencies (Mendell 1966;Schouenborg and Dickenson 1988) or by nerve and tissue injury (Kenshalo et al 1982;Woolf 1984;Wall and Woolf 1985;Woolf and Wall 1986;Haley et al 1990;Sher and Mitchell 1990;Owens et al 1992) is known to sensitize dorsal horn neurons.…”

Absence of Thermal Hyperalgesia in Serotonin Transporter-Deficient Mice

“…This normally takes place at the receptor site on the sensory terminal (Raja et al, 1999). After nerve lesion, the injured axons themselves can be activated and sensitized by inflammatory mediators (Welk et al, 1990;Michaelis et al, 1997Michaelis et al, , 1998. We hypothesize that 5-HT in the injured nerve sensitizes nociceptive nerve fibers to heat stimuli, thus leading to heat hyperalgesia, and that the low 5-HT concentration in 5-HTTϪ/Ϫ mice is the reason for the lack of heat hyperalgesia in these mice.…”

Voltage‐gated sodium channels as molecular targets for neuropathic pain

“…When the injury involves damage to a nerve trunk or the spinal nerves, the effect is to create a focal or ''ectopic'' area of hyperexcitability by localized membrane remodeling [reviewed by Devor and Seltzer, 2000]. Pathological hyperexcitability increases impulse traffic along the affected nerve trunk and this has been detected in numerous experimental and clinical studies [Abdulla and Smith, 2001;Burchiel, 1980a,b;Burchiel et al, 1985;Calvin et al, 1982;Campero et al, 1998;Chul Han et al, 2000;Devor and Seltzer, 2000;Eliav et al, 2001;Govrin-Lippmann and Devor, 1978;Gracely et al, 1992;Han et al, 2000;Kajander et al, 1992;Liu et al, 2000aLiu et al, ,b, 2001Stebbing et al, 1999;Tal et al, 1999;Wall and Gutnick, 1974;Welk et al, 1990;Wu et al, 2001Wu et al, , 2002Yates et al, 2000]. There is also evidence for axonal hyperexcitability inducing subsequent changes in excitability at the cell bodies within the sensory ganglia [Kajander et al, 1992;Liu et al, 2000a] that may persist after resection of distal ectopic foci [Liu et al, 2000a].…”