Inflammatory mediators enhance the excitability of chronically compressed dorsal root ganglion neurons.

A laterally herniated disk, spinal stenosis, and various degenerative or traumatic diseases of the spine can sometimes lead to a chronic compression and inflammation of the dorsal root ganglion and chronic abnormal sensations including pain. After a chronic compression of the dorsal root ganglion (CCD) in rats, the somata in the dorsal root ganglion (DRG) become hyperexcitable, and some exhibit ectopic, spontaneous activity (SA). Inflammatory mediators have a potential role in modulating the excitability of DRG neurons and therefore may contribute to the neuronal hyperexcitability after CCD. In this study, an inflammatory soup (IS) consisting of bradykinin, serotonin, prostaglandin E2, and histamine (each 10(-6) M) was applied topically to the DRG. The responses of DRG neurons were electrophysiologically recorded extracellularly from teased dorsal root fibers or intracellularly from the somata in the intact DRG or from dissociated neurons within 30 h of culture. In all three preparations, IS remarkably increased the discharge rates of SA CCD neurons and evoked discharges in more silent-CCD than control neurons. IS slightly depolarized the resting membrane potential and decreased the current and voltage thresholds of action potential in both intact and dissociated neurons, although the magnitude of depolarization or decrease in action potential threshold was not significantly different between CCD and control. IS-evoked responses were found in a proportion of neurons in each size category including those with and without nociceptive properties. Inflammatory mediators, by increasing the excitability of DRG somata, may contribute to CCD-induced neuronal hyperexcitability and to hyperalgesia and tactile allodynia.

Mechanical and thermal hyperalgesia and ectopic neuronal discharge after chronic compression of dorsal root ganglia.

Chronic compression of the dorsal root ganglion (CCD) was produced in adult rats by implanting a stainless steel rod unilaterally into the intervertebral foramen, one rod at L(4) and another at L(5). Two additional groups of rats received either a sham surgery or an acute injury consisting of a transient compression of the ganglion. Withdrawal of the hindpaw was used as evidence of a nocifensive response to mechanical and thermal stimulation of the plantar surface. In addition, extracellular electrophysiological recordings of spontaneous discharges were obtained from dorsal root fibers of formerly compressed ganglia using an in vitro nerve-DRG-dorsal root preparation. The mean threshold force of punctate indentation and the mean threshold temperature of heating required to elicit a 50% incidence of foot withdrawal ipsilateral to the CCD were significantly lower than preoperative values throughout the 35 days of postoperative testing. The number of foot withdrawals ipsilateral to the CCD during a 20-min contact with a temperature-controlled floor was significantly increased over preoperative values throughout postoperative testing when the floor was 4 degrees C (hyperalgesia) and, to a lesser extent, when it was 30 degrees C (spontaneous pain). Stroking the foot with a cotton wisp never elicited a reflex withdrawal before surgery but did so in most rats tested ipsilateral to the CCD during the first 2 postoperative weeks. In contrast, the CCD produced no changes in responses to mechanical or thermal stimuli on the contralateral foot. The sham operation and acute injury produced no change in behavior other than slight, mechanical hyperalgesia for approximately 1 day, ipsilateral to the acute injury. Ectopic spontaneous discharges generated within the chronically compressed ganglion and, occurring in the absence of blood-borne chemicals and without an intact sympathetic nervous system, were recorded from neurons with intact, conducting, myelinated or unmyelinated peripheral nerve fibers. The incidence of spontaneously active myelinated fibers was 8.61% for CCD rats versus 0.96% for previously nonsurgical rats. We hypothesize that a chronic compression of the dorsal root ganglion after certain injuries or diseases of the spine may produce, in neurons with intact axons, abnormal ectopic discharges that originate from the ganglion and potentially contribute to low back pain, sciatica, hyperalgesia, and tactile allodynia.