Electrophysiological and molecular characteristics of SP-mediated antinociception in muscle nociceptors
| Autor: | Chu-Ting Chang, 張筑婷 |
|---|---|
| Rok vydání: | 2017 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 105 Previous study demonstrated that acid trigger substance P (SP) release and produced antinociceptive effect in muscle nociceptors, by which SP specifically enhances M-type potassium current and attenuates ASIC3-induced inward current on most gastrocnemius muscle (GM) afferent dorsal root ganglion (DRG) neurons Furthermore, previous study also indicated that the analgesia effect of T1-11, an active ingredient from Gastrodia elata for pain management, is ineffective in ASIC3 KO mice after intermittent cold stress (ICS) treatment and T1-11-induced outward current can be attenuated by NK1 antagonist. Therefore, I aimed to probe whether ASIC3 contributes to SP-mediated antinociception. Firstly, I identified the molecular identity of muscle afferent DRG neurons by use of single cell RT-PCR. The co-expression of SP with ASIC3 or TRPV1 implied the possibility that ASIC3 and TRPV1 serve as the antinociceptive acid sensors that release SP. Besides, I aimed to know whether loss of ASIC3 affects SM-SP-, a synthesized peptide analog of SP, and T1-11-induced outward current (ISM-SP-O and IT1-11-O) in muscle afferent DRG neurons by use of whole-cell patch clamp recording. The result demonstrated that deletion of ASIC3 did not affect neuronal population and average peak current of ISM-SP-O. However, I found diminished neuronal population of IT1-11-O after loss of ASIC3 in naïve but not ICS-treated mice. Furthermore, I found increased action potential (AP) threshold after deletion of ASIC3 and revealed a role of ASIC3 in setting the AP threshold. On the other hand, increased average peak current of ISM-SP-O was found in muscle afferent DRG neurons after ICS treatment, which suggests an enhanced SP-mediated antinociception. Besides, elevated AP overshoot was observed after ICS treatment in a subset of neurons that do not respond to SM-SP. Because large overshoot has been implicated as a feature of nociceptors, elevated overshoot after ICS treatment may indicate a pronociceptive neuronal plasticity occurred in these neurons. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
| Externí odkaz: |
|