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AuthorDjouhri, Laiche
AuthorZeidan, Asad
AuthorAbd El-Aleem, Seham A
AuthorSmith, Trevor
Available date2020-06-21T06:54:50Z
Publication Date2020
Publication NameFrontiers in Neuroscience
Identifierhttp://dx.doi.org/10.3389/fnins.2020.00530
CitationDjouhri L, Zeidan A, Abd El-Aleem SA and Smith T (2020) Cutaneous Aβ-Non-nociceptive, but Not C-Nociceptive, Dorsal Root Ganglion Neurons Exhibit Spontaneous Activity in the Streptozotocin Rat Model of Painful Diabetic Neuropathy in vivo. Front. Neurosci. 14:530. doi: 10.3389/fnins.2020.00530
ISSN1662-4548
URIhttp://hdl.handle.net/10576/15076
AbstractDiabetic peripheral neuropathic pain (DPNP) is the most devastating complication of diabetes mellitus. Unfortunately, successful therapy for DPNP remains a challenge because its pathogenesis is still elusive. However, DPNP is believed to be due partly to abnormal hyperexcitability of dorsal root ganglion (DRG) neurons, but the relative contributions of specific functional subtypes remain largely unknown. Here, using the strepotozotocin (STZ) rat model of DPNP induced by a STZ injection (60 mg/kg, i.p), and intracellular recordings of action potentials (APs) from DRG neurons in anesthetized rats, we examined electrophysiological changes in C-and Aβ-nociceptive and Aβ-low threshold mechanoreceptive (LTM) neurons that may contribute to DPNP. Compared with control, we found in STZ-rats with established pain hypersensitivity (5 weeks post-STZ) several significant changes including: (a) A 23% increase in the incidence of spontaneous activity (SA) in Aβ-LTMs (but not C-mechanosensitive nociceptors) that may cause dysesthesias/paresthesia suffered by DPNP patients, (b) membrane hyperpolarization and a ∼85% reduction in SA rate in Aβ-LTMs by K7 channel activation with retigabine (6 mg/kg, i.v.) suggesting that K7/M channels may be involved in mechanisms of SA generation in Aβ-LTMs, (c) decreases in AP duration and in duration and amplitude of afterhyperpolarization (AHP) in C-and/or Aβ-nociceptors. These faster AP and AHP kinetics may lead to repetitive firing and an increase in afferent input to the CNS and thereby contribute to DPNP development, and (d) a decrease in the electrical thresholds of Aβ-nociceptors that may contribute to their sensitization, and thus to the resulting hypersensitivity associated with DPNP.
SponsorThis research work was supported by a Medical Research Council grant (G0700420) and a Ph.D. studentship from Biotechnology and Biological Sciences Research Council to LD.
Languageen
PublisherFrontiers Media
SubjectK+ channels
action potential
diabetic neuropathy
nociception
primary sensory neurons
TitleCutaneous Aβ-Non-nociceptive, but Not C-Nociceptive, Dorsal Root Ganglion Neurons Exhibit Spontaneous Activity in the Streptozotocin Rat Model of Painful Diabetic Neuropathy .
TypeArticle
Volume Number14
ESSN1662-453X
dc.accessType Open Access


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