Archives

  • 2018-07
  • 2018-10
  • 2018-11
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • NO has been shown to

    2021-11-22

    NO has been shown to be necessary for long-term potentiation (LTP) of GABAergic neurons in the amygdala (Lange et al., 2012), the hippocampus (Zhuo et al., 1993), the ventral tegmental area (VTA) (Nugent et al., 2009), and the spinal cord (Fenselau et al., 2011). NO is also known to increase GABA release from presynaptic ha141 by increasing calcium in the presynaptic cells as well as through the sodium-dependent carrier GABA uptake system (Kuriyama and Ohkuma, 1995). HBO2-induced antinociception has been shown to be mediated by a NO-sGC-cGMP-PKG pathway (Ding et al., 2017, Quock et al., 2011). The same signaling pathway is involved in NO enhancement of GABA release in the basolateral complex of the amygdala (Lange et al., 2012). The objective of the present investigation was to assess the possible involvement of GABAergic mechanisms in the acute antinociceptive effect of HBO2 in a mouse model of acute pain and to provide neuroanatomical evidence for interactions of brainstem nociceptive GABAergic pathways with HBO2. It is likely that HBO2-induced acute antinociception is partially mediated by GABA transmission in the spinal cord. HBO2 can potentially increase NO, which, in turn, increases GABA activity, which contributes to the acute antinociceptive effect of HBO2.
    Results
    Discussion The purpose of this study was to investigate a possible role for spinal cord GABA in a model of HBO2-induced acute antinociception using a combination of pharmacological, behavioral and molecular biology methods. The GABAA antagonist SR 95531 attenuated HBO2-induced acute antinociception in a dose-dependent manner at very low doses (nanomolar range), thus implicating GABAA receptors in HBO2-induced antinociception. We were also able to enhance HBO2-induced antinociception by pretreating with nipecotic acid, an inhibitor of the GABA reuptake transporter (Johnston et al., 1979). This indicates that the synaptic levels of GABA are positively correlated with the magnitude of the HBO2-induced acute antinociceptive effect. A role for the GABAB receptor was discounted as the doses of CGP 35348 used failed to affect the antinociceptive effect of HBO2. CGP 35348 alone also produced no change in abdominal constrictions. We conclude that spinal GABAB receptors are not involved in HBO2-induced acute antinociception in mice, although it is possible that the doses used were too low to influence the antinociceptive effect of HBO2. However, CGP 35348 doses comparable to ours administered into the mouse lateral cerebral ventricle antagonized (±)-baclofen-induced antinociception in the abdominal constriction test (Malcangio et al., 1991). It is possible that this dose is not high enough when administered into the thecal space compared to ventricular space. Unpublished data from our lab indicates that this might not be the case as intracerebroventricular administration of the same doses of CGP35348 also failed to block HBO2. This evidence supports the supposition that antagonism of the GABAB receptor does not affect antinociception under HBO2. Previously, we demonstrated that the antinociceptive effect of an 11-min HBO2 treatment was modulated in part by both NO and opioid mechanisms (Heeman et al., 2013, Ohgami et al., 2009, Quock et al., 2011). Our current results indicate that acetic acid decreases nNOS expression in the lumbar spinal cord and this effect is not as prevalent in animals treated with HBO2. In another study, it was observed that a 60-min treatment of HBO2 increased levels of NO oxidation products in the spinal cord of adult rats (Ohgami et al., 2008). Furthermore, the involvement of NO was verified by dose-related antagonism of HBO2-induced antinociception by i.t. administered nitric oxide synthase (NOS) inhibitors and attenuation of the HBO2 effect by using nNOS knockout mice and antisense oligodeoxynucleotides to nNOS to knock down NOS (Ohgami et al., 2009). Our current results indicate that GABA acting at the GABAA receptor in the spinal cord may also be involved in the HBO2 induced antinociception. Our current results do not conclusively link HBO2 effects on nNOS to effects HBO2 may have on GABA although previous studies have indicated that nNOS and may influence GABAergic signaling. GABA localization studies indicate the presence of many GABAergic interneurons in the spinal cord, especially in the superficial lamina (Sardella et al., 2011). In particular, co-localized nNOS- and GABA-immunoreactive neurons have been found in lamina I and lamina II, and nNOS was found in terminal boutons containing vesicular GABA transporters (Sardella et al., 2011). Therefore, this is a possible pathway in which GABA may interact with the NO-sGC-cGMP pathway, which has been implicated in HBO2-induced antinociception (Ding et al., 2017, Quock et al., 2011).