α-Dendrotoxin-sensitive Kv1 channels contribute to conduction failure of polymodal nociceptive C-fibers from rat coccygeal nerve

Wang, Xiuchao; Wang, Shan; Zhang, Ming; Gao, Fang; Yin, Chun; Li, Hao; Zhang, Ying; Hu, San-Jue; Duan, Jian-Hong

doi:10.1152/jn.00786.2014

Cited by 18 publications

(11 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Altered peripheral nerve function in the rat model of paclitaxel‐induced neuropathy has been demonstrated with in vivo electrophysiological recordings revealing that ~30% of C‐fibres display spontaneous activity that is reduced by prophylactic treatment with acetyl‐ l ‐carnitine, which is known to limit mitochondrial dysfunction . Altered C‐fibre function can also be characterized, in both preclinical pain models and chronic pain patients, by measuring the phenomenon of C‐fibre ADS, which is a progressive slowing of nociceptive C‐fibre conduction velocity in response to repetitive stimulation . However, to date, this had not been addressed for CINP.…”

Section: Discussionmentioning

confidence: 99%

Melatonin limits paclitaxel‐induced mitochondrial dysfunction in vitro and protects against paclitaxel‐induced neuropathic pain in the rat

Galley

McCormick

Wilson

et al. 2017

Journal of Pineal Research

View full text Add to dashboard Cite

Chemotherapy‐induced neuropathic pain is a debilitating and common side effect of cancer treatment. Mitochondrial dysfunction associated with oxidative stress in peripheral nerves has been implicated in the underlying mechanism. We investigated the potential of melatonin, a potent antioxidant that preferentially acts within mitochondria, to reduce mitochondrial damage and neuropathic pain resulting from the chemotherapeutic drug paclitaxel. In vitro, paclitaxel caused a 50% reduction in mitochondrial membrane potential and metabolic rate, independent of concentration (20‐100 μmol/L). Mitochondrial volume was increased dose‐dependently by paclitaxel (200% increase at 100 μmol/L). These effects were prevented by co‐treatment with 1 μmol/L melatonin. Paclitaxel cytotoxicity against cancer cells was not affected by co‐exposure to 1 μmol/L melatonin of either the breast cancer cell line MCF‐7 or the ovarian carcinoma cell line A2780. In a rat model of paclitaxel‐induced painful peripheral neuropathy, pretreatment with oral melatonin (5/10/50 mg/kg), given as a daily bolus dose, was protective, dose‐dependently limiting development of mechanical hypersensitivity (19/43/47% difference from paclitaxel control, respectively). Melatonin (10 mg/kg/day) was similarly effective when administered continuously in drinking water (39% difference). Melatonin also reduced paclitaxel‐induced elevated 8‐isoprostane F2α levels in peripheral nerves (by 22% in sciatic; 41% in saphenous) and limited paclitaxel‐induced reduction in C‐fibre activity‐dependent slowing (by 64%). Notably, melatonin limited the development of mechanical hypersensitivity in both male and female animals (by 50/41%, respectively), and an additive effect was found when melatonin was given with the current treatment, duloxetine (75/62% difference, respectively). Melatonin is therefore a potential treatment to limit the development of painful neuropathy resulting from chemotherapy treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

Melatonin limits paclitaxel‐induced mitochondrial dysfunction in vitro and protects against paclitaxel‐induced neuropathic pain in the rat

Galley

McCormick

Wilson

et al. 2017

Journal of Pineal Research

View full text Add to dashboard Cite

show abstract

“…Furthermore, there is reduced ADS in a diabetic neuropathic pain model (Wang et al, 2016b). In contrast, there is enhanced ADS in the spinal nerve ligation model of neuropathic pain (Shim et al, 2007), but these findings need to be considered within a partially denervated pain circuitry.…”

Section: Discussionmentioning

confidence: 99%

Inflammatory Pain Reduces C Fiber Activity-Dependent Slowing in a Sex-Dependent Manner, Amplifying Nociceptive Input to the Spinal Cord

et al. 2017

View full text Add to dashboard Cite

C fibers display activity-dependent slowing (ADS), whereby repetitive stimulation (≥1 Hz) results in a progressive slowing of action potential conduction velocity, which manifests as a progressive increase in response latency. However, the impact of ADS on spinal pain processing has not been explored, nor whether ADS is altered in inflammatory pain conditions. To investigate, compound action potentials were made, from dorsal roots isolated from rats with or without complete Freund's adjuvant (CFA) hindpaw inflammation, in response to electrical stimulus trains. CFA inflammation significantly reduced C fiber ADS at 1 and 2 Hz stimulation rates. Whole-cell patch-clamp recordings in the spinal cord slice preparation with attached dorsal roots also demonstrated that CFA inflammation reduced ADS in the monosynaptic C fiber input to lamina I neurokinin 1 receptor-expressing neurons (1–10 Hz stimulus trains) without altering the incidence of synaptic response failures. When analyzed by sex, it was revealed that females display a more pronounced ADS that is reduced by CFA inflammation to a level comparable with males. Cumulative ventral root potentials evoked by long and short dorsal root stimulation lengths, to maximize and minimize the impact of ADS, respectively, demonstrated that reducing ADS facilitates spinal summation, and this was also sex dependent. This finding correlated with the behavioral observation of increased noxious thermal thresholds and enhanced inflammatory thermal hypersensitivity in females. We propose that sex/inflammation-dependent regulation of C fiber ADS can, by controlling the temporal relay of nociceptive inputs, influence the spinal summation of nociceptive signals contributing to sex/inflammation-dependent differences in pain sensitivity.SIGNIFICANCE STATEMENT The intensity of a noxious stimulus is encoded by the frequency of action potentials relayed by nociceptive C fibers to the spinal cord. C fibers conduct successive action potentials at progressively slower speeds, but the impact of this activity-dependent slowing (ADS) is unknown. Here we demonstrate that ADS is more prevalent in females than males and is reduced in an inflammatory pain model in females only. We also demonstrate a progressive delay of C fiber monosynaptic transmission to the spinal cord that is similarly sex and inflammation dependent. Experimentally manipulating ADS strongly influences spinal summation consistent with sex differences in behavioral pain thresholds. This suggests that ADS provides a peripheral mechanism that can regulate spinal nociceptive processing and pain sensation.

show abstract

“…Whole-cell potassium currents were recorded according to the protocols reported in previous studies ( Bekkers, 2000 ; Brew et al, 2003 ; Itri et al, 2005 ; Wang et al, 2016b ; Yang et al, 2010 ). The internal solution was the same as above.…”

Section: Methodsmentioning

confidence: 99%

Severe deficiency of the voltage-gated sodium channel NaV1.2 elevates neuronal excitability in adult mice

et al. 2021

View full text Add to dashboard Cite

show abstract

α-Dendrotoxin-sensitive Kv1 channels contribute to conduction failure of polymodal nociceptive C-fibers from rat coccygeal nerve

Abstract: SJ, Duan JH. ␣-Dendrotoxin-sensitive Kv1 channels contribute to conduction failure of polymodal nociceptive C-fibers from rat coccygeal nerve.

Cited by 18 publications

References 41 publications

Melatonin limits paclitaxel‐induced mitochondrial dysfunction in vitro and protects against paclitaxel‐induced neuropathic pain in the rat

Melatonin limits paclitaxel‐induced mitochondrial dysfunction in vitro and protects against paclitaxel‐induced neuropathic pain in the rat

Inflammatory Pain Reduces C Fiber Activity-Dependent Slowing in a Sex-Dependent Manner, Amplifying Nociceptive Input to the Spinal Cord

Severe deficiency of the voltage-gated sodium channel NaV1.2 elevates neuronal excitability in adult mice

Contact Info

Product

Resources

About