Multiple Sites for Generation of Ectopic Spontaneous Activity in Neurons of the Chronically Compressed Dorsal Root Ganglion

Abstract

In a chronically compressed dorsal root ganglion (CCD) in the rat, a model of foraminal stenosis and radicular pain in human, a subpopulation of neurons with functional axons exhibits spontaneous activity (SA) that originates within the ganglion. Intracellular electrophysiological recordings were obtained from the somata of neurons of the compressed ganglion both in vitro and in vivo. The SA was classified into two types according to the presence (type I) or absence (type II) of subthreshold membrane potential oscillation. Neurons with type I SA had significantly higher somal excitability than those with type II SA. In most cases, depolarization of the membrane potential by current injection increased the discharge rates of type I -but not type II SA. Both types occasionally coexisted in the same neuron. Several lines of evidence suggested that the origin of SA in the DRG was most likely the soma for type I SA and the axon for type II. Therefore CCD neurons have multiple sites for generation of action potentials other than the terminal endings. In vivo recordings revealed the same two types of SA in a subpopulation of neurons with functionally characterized peripheral receptive fields. Thus, SA might not only produce spurious sensory input to the afferent pathways but also add to or block impulse transmission generated by natural stimulation of peripheral receptors. SA originating in the compressed ganglion is likely to interfere with sensory transmission in nociceptive and non-nociceptive neurons, thereby contributing to radicular pain, paresthesias, hyperalgesia and allodynia.

Sigma-1 Receptor Antagonist BD1047 Reduces Allodynia and Spinal ERK Phosphorylation Following Chronic Compression of Dorsal Root Ganglion in Rats

“…Foraminal stenosis encompasses some of the most common and popular reasons that are used to explain acute and chronic sciatica. Under CCD conditions, spontaneous action potentials can originate from multiple locations in both the soma and the axons of the DRG neurons and these spontaneous action potentials may alter the transmission of sensory information from peripheral receptors [12]. According to this etiology, the paw withdrawal frequency by either mechanical or cold stimuli was significantly increased following CCD surgery as compared with that of the sham operative animals in our study.…”

“…Several lines of evidence have suggested that the origin of spontaneous activity in the CCD was most likely the soma rather than the axons or the terminal endings [12]. Differing alterations of sodium currents in small dorsal root ganglion neurons have also been observed after CCD and sciatic nerve injury [9].…”

“…Under anesthesia by an intraperitoneal injection mixture of ketamine (90 mg/kg) and xylazine (9 mg/kg), the transverse process and intervertebral foramina of L4 and L5 were exposed unilaterally as previously described [12]. A stainless steel L shaped rod (0.63 mm in diameter and 4 mm in length) was inserted into each foramen, one at L4 and the other at the L5 ganglion.…”

NAD+Activates KNaChannels in Dorsal Root Ganglion Neurons

“…As we have now shown, K Na channels are abundantly and ubiquitously expressed in DRG neurons. Since both propioceptors and nociceptors are believed to contribute to painful neuropathy (Amir et al, 1999;Ma and LaMotte, 2007), K Na channel dysfunctioning may be a likely culprit in the pathology of neuropathic pain. Alternatively, increasing K Na channel activity may also represent a therapeutic strategy for the treatment of neuropathic pain.…”

In vivo responses of cutaneous C-mechanosensitive neurons in mouse to punctate chemical stimuli that elicit itch and nociceptive sensations in humans

“…The base plate holding the animal was then mounted to a frame under the objective of an upright microscope (BX51WI; Olympus Optical, Tokyo, Japan). The neurons on the surface of DRG were viewed through a ϫ40 water-immersion objective (magnification ϫ400) using reflective microscopy via an analyzer-50/50 mirror-polarizer set (Ma and LaMotte 2007). The DRG was continuously superfused by oxygenated ACSF at a rate of 3 ml/min, and the temperature was maintained at 37 Ϯ 0.5°C via an in-line heater (TC-344A; Warner Instrument, Hamden, CT).…”