An electrophysiological study of dorsal horn neurons in the spinal cord of rats with an experimental peripheral neuropathy

Abstract

1. Extracellular single-unit recordings have been made from 295 dorsal horn neurons in the lumbar enlargement of rat spinal cord; 191 neurons in 20 rats with an experimental peripheral neuropathy, and 104 in 10 sham-operated rats. Recordings were made 9-11 days after inducing the neuropathy by tying four loose ligatures around the sciatic nerve in the nerve-injured rats or performing a sham procedure in the sham-operated rats. 2. A survey of the general properties of all neurons encountered was made in the 10 sham-operated rats (104 neurons) and compared with those seen in 17 of the nerve-injured animals (180 neurons). The vast majority (87%; 156/180) of neurons recorded in the nerve-injured animals showed abnormal characteristics; these included responses to very gentle mechanical stimulation of the nerve-injury site and to manipulations that resulted in movement of this site such as extension of the leg and probing of the skin and muscle of the thigh (53%), absence of detectable peripheral receptive fields (RFs; 56%), and very high spontaneous activity (7%). In the sham-operated rats none of the neurons recorded could be activated by gentle mechanical stimulation of the sciatic nerve, and only 6% had no detectable peripheral RF. 3. In the nerve-injured animals, 31% (55/180) of cells had both a peripheral RF, and a response to gentle mechanical stimulation of the nerve-injury site. All cells of this type tested (n = 5) showed very prolonged responses (up to 10 min long) to 15 s pinch stimuli applied to the RF and to 15 s gentle tapping of the injury site. The majority of cells in this group were excited by noxious stimuli (71%; 39/55) and had C-fiber inputs (60%; 33/55). 4. The mean threshold temperatures for evoking responses to heat stimuli in cells tested in nerve-injured rats and in sham-operated animals were not different. However, there was a group of neurons in the nerve-injured rats that had low thresholds, failed to encode stimulus intensity, and did not have a C-fiber input. 5. There were significantly fewer neurons excited by low-intensity stimulation of the skin in the nerve-injured (24%; 43/180) than in the sham-operated rats (71%; 74/104). Measurements of mechanical threshold with von Frey hairs showed that, although the mean threshold did not change, none of the cells tested in the nerve-injured animals had thresholds < 12 mN, whereas the lowest threshold recorded in the sham-operated animals was 0.2 mN.(ABSTRACT TRUNCATED AT 400 WORDS)

Plasticity in intact Aδ- and C-fibers contributes to cold hypersensitivity in neuropathic rats

“…Finally, calcium imaging studies confirm an increase in percentage and magnitude of response of L4 DRG cells to icilin in SNL compared with naive rats. Although dorsal horn neurons in neuropathic rats show increased activity to mechanical and cold stimulation of the nerve-injured limb (Palecek et al, 1992a,b;Laird and Bennett, 1993), the present data indicate that changes in primary afferent fibers are the driving force for these central changes. Mechanical allodynia in SNL rats.…”

“…Dorsal horn neurons show increased background activity and enhanced activity following mechanical (Palecek et al, 1992a,b;Laird and Bennett, 1993). However, there is substantial evidence that primary afferents, both injured and uninjured, play a major role in the expression of the sensory abnormalities following nerve injury (Ringkamp and Meyer, 2005).…”

Altered Sodium Channel Expression in Second-Order Spinal Sensory Neurons Contributes to Pain after Peripheral Nerve Injury

“…First, as early as 3 d after injury, ectopic discharges and abnormal responses to stimuli originate in the injured axons and their cells of origin within the DRG (Wall and Gutnick, 1974;Govrin-Lippmann and Devor, 1978;Scadding, 1981;Wall and Devor, 1983;Kajander et al, 1992;Kral et al, 1999) and are expected to drive dorsal horn neurons to relay higher-frequency afferent information supraspinally. Second, dorsal horn neurons undergo reactive changes that make them hyperresponsive, and abnormal firing has been shown to originate from within the dorsal horn after peripheral injury (Basbaum and Wall, 1976;Woolf, 1983;Woolf and Wall, 1986;Palecek et al, 1992;Sotgiu et al, 1992;Laird and Bennett, 1993). Activity-dependent central sensitization (heterosynaptic facilitation) is evident within seconds of a nociceptive conditioning stimulus and can outlast the stimulus for hours (Woolf and Wall, 1986).…”

“…Injury of peripheral nerves can result in the development of a chronic neuropathic pain syndrome associated with hyperresponsiveness of sensory neurons within the dorsal root ganglion (DRG) (Wall and Devor, 1983;Study and Kral, 1996) and the spinal cord dorsal horn (Woolf, 1983;Sotgiu et al, 1992;Laird and Bennett, 1993).…”

Long-term changes in behavior and regional cerebral blood flow associated with painful peripheral mononeuropathy in the rat

“…The abnormalities in the activity of dorsal horn cells have been observed: some neurons present spontaneous activity and/or long after-discharges (Hylden et al, 1987;Palecek et al, 1992;Laird and Bennett, 1993;Sotgiu et al, 1995). An increase in spinal and supraspinal neuronal activity as estimated by the [ 14 C]2-deoxyglucose technique has also been reported with the chronic constriction injury (CCI) model (Mao et al, 1992a(Mao et al, , 1993.…”