Subthreshold Oscillations Induced By Spinal Nerve Injury In Dissociated Muscle And Cutaneous Afferents Of Mouse DRG

Abstract

Whole cell patch-clamp recordings were obtained from dissociated mouse lumbar dorsal root ganglion (DRG) neurons. Recordings were made from control neurons and neurons axotomized by transection of the corresponding spinal nerve 1-2 days prior to dissociation. Medium to large muscle and cutaneous afferent neurons were identified by retrograde transport of True Blue or Fluoro-Gold injected into the corresponding peripheral tissue. Action potentials were classified as non-inflected spikes (A 0 ) and inflected spikes (A inf ). High-frequency, low-amplitude subthreshold membrane potential oscillations were observed in 8% of control A 0 neurons, but their incidence increased to 31% in the nerve injury group. Fifty percent of axotomized muscle afferent A 0 cells displayed oscillations, while 26% of axotomized cutaneous afferents exhibited oscillations. Lower-frequency oscillations were also observed in a small fraction (4%) of A inf neurons on strong depolarization. Their numbers were increased after the nerve injury, but the difference was not statistically significant. The oscillations often triggered burst firing in distinct patterns of action potential activity. These results indicate that injury-induced membrane oscillations of DRG neurons, previously observed in whole DRG of rats, are present in dissociated DRG neurons of the adult mouse. Moreover, these observations indicate that both muscle and cutaneous afferents in the A β size range give rise to injury-induced membrane oscillations, with muscle afferents being more prone to develop oscillations.

Contribution of primary afferent channels to neuropathic pain

“…Based on the unique biophysical properties of Na v 1.3 and the dramatic increase in expression of this channel in injured neurons, this channel was a good candidate for the channel underlying membrane oscillations. A more detailed biophysical analysis of the oscillatory behavior, which is increased with membrane depolarization well above −40 mV [33], suggested this channel may not contribute to the oscillatory behavior as originally suspected. Given mixed results with antisense knockdown of the channel [1], its contribution to neuropathic pain remains in question.…”

Using dynamic clamp to quantify pathological changes in the excitability of primary somatosensory neurons

“…) or to respond to sustained depolarization with repetitive spiking (Liu et al . ; Ratté et al . ) after nerve injury.…”

“…), but, under conditions associated with chronic pain, some neurons develop the capacity to spike repetitively during sustained depolarization (Liu et al . , ; Xing et al . ; Ma & LaMotte, ; Fan et al .…”

K+ current regulates calcium‐activated chloride current‐induced afterdepolarization in axotomized sensory neurons

“…We focused on medium‐sized neurons from a mixed population of A‐δ and A‐β neurons that include high‐ and low‐threshold mechanoreceptors. Following injury, these subpopulations display an increase in excitability in vivo , which is preserved in dissociated sensory neurons (Liu et al ., 2002; Ma & LaMotte, 2005) like those in our model (Hilaire et al ., 2005), and specifically upregulate the expression of ICl(Ca) (Andre et al ., 2003a). We show here that a sustained increase in Ca 2+ i , by increasing stimulation frequency or AP duration, is required to activate ICl(Ca).…”