Search

Background and Purpose: Hydrogen sulfide, a gasotransmitter, facilitates somatic pain signals via activation of Ca(v)3.2 T-type calcium channels in rats. Given evidence for the activation of transient receptor potential ankyrin-1 (TRPA1) channels by H(2)S, we asked whether TRPA1 channels, in addition to Ca(v)3.2 channels, contribute to the H(2)S-induced mechanical hyperalgesia and allodynia in mice.Experimental Approach: Mechanical hyperalgesia and allodynia were evaluated by the von Frey test in mice. Ca(v)3.2 or TRPA1 channels in the sensory neurons were silenced by repeated intrathecal administration of antisense oligodeoxynucleotides in mice.Key Results: Intraplantar administration of NaHS evoked hyperalgesia and allodynia in mice, an effect attenuated or abolished by NNC 55-0396 or mibefradil, T-type calcium channel blockers, and by ascorbic acid or zinc chloride, known to selectively inhibit Ca(v)3.2 channels, out of the three isoforms of T-type calcium channels. Silencing of Ca(v)3.2 channels in the sensory neurons also prevented the NaHS-induced hyperalgesia and allodynia in mice. The NaHS-induced hyperalgesia and allodynia in mice were significantly suppressed by AP18, a TRPA1 channel blocker, and by silencing of TRPA1 channels in the sensory neurons.Conclusions and Implications: Mechanical hyperalgesia and allodynia induced by NaHS/H(2)S required activation of both Ca(v)3.2 and TRPA1 channels in mice. [ABSTRACT FROM AUTHOR]

[Purpose] The soleus H-reflex is depressed at stimulation rates greater than 0.1 Hz. This reflex depression is referred to as postactivation depression. Postactivation depression reflects the reduced efficacy of the Ia-motoneurons synapses when they are evaluated after a previous activation. The aim of this study was to determine whether the recovery of motor functions in the lower extremities affects the PAD of the soleus H-reflex in patients with subacute stroke undergoing rehabilitation. [Subjects and Methods] Eight patients with subacute stroke patients were recruited. Postactivation depression, Fugl-Meyer score (lower-limb portion), walking velocity, the Modified Ashworth Scale, and center of pressure sway during standing were measured within three days of admission to rehabilitation and 50 days later. [Results] After rehabilitation, Fugl-Meyer scores, center of pressure path length, and walking velocity were significantly improved, and postactivation depression had significantly increased. There was a significant positive correlation between the rates of change of postactivation depression and center of pressure path length. [Conclusion] The results demonstrated that postactivation depression is partially normalized after rehabilitation in patients with subacute stroke, and suggested that the recovery in lower extremity function after stroke particularly standing stability is affected by spinal synaptic plasticity.

T-type Ca channels (T channels), particularly Cav3.2 among the 3 isoforms, play a role in neuropathic and visceral pain. We thus characterized the effects of RQ-00311651 (RQ), a novel T-channel blocker, in HEK293 cells transfected with human Cav3.1 or Cav3.2 by electrophysiological and fluorescent Ca signaling assays, and also evaluated the antiallodynic/antihyperalgesic activity of RQ in somatic, visceral, and neuropathic pain models in rodents. RQ-00311651 strongly suppressed T currents when tested at holding potentials of -65 ∼ -60 mV, but not -80 mV, in the Cav3.1- or Cav3.2-expressing cells. RQ-00311651 also inhibited high K-induced Ca signaling in those cells. In mice, RQ, administered intraperitoneally (i.p.) at 5 to 20 mg/kg or orally at 20 to 40 mg/kg, significantly suppressed the somatic hyperalgesia and visceral pain-like nociceptive behavior/referred hyperalgesia caused by intraplantar and intracolonic administration of NaHS or Na2S, H2S donors, respectively, which involve the enhanced activity of Cav3.2 channels. RQ-00311651, given i.p. at 5 to 20 mg/kg, exhibited antiallodynic or antihyperalgesic activity in rats with spinal nerve injury-induced neuropathy or in rats and mice with paclitaxel-induced neuropathy. Oral and i.p. RQ at 10 to 20 mg/kg also suppressed the visceral nociceptive behavior and/or referred hyperalgesia accompanying cerulein-induced acute pancreatitis and cyclophosphamide-induced cystitis in mice. The analgesic and antihyperalgesic/antiallodynic doses of oral and i.p. RQ did not significantly affect the locomotor activity and motor coordination. Together, RQ is considered a state-dependent blocker of Cav3.1/Cav3.2 T channels and may serve as an orally available analgesic for treatment of neuropathic and inflammatory pain including distinct visceral pain with minimum central side effects.

Given that high mobility group box 1 (HMGB1), a nuclear protein, once released to the extracellular space, promotes nociception, we asked if inactivation of HMGB1 prevents or reverses chemotherapy-induced painful neuropathy in rats and also examined possible involvement of Toll-like receptor 4 (TLR4) and the receptor for advanced glycation endproduct (RAGE), known as targets for HMGB1. Painful neuropathy was produced by repeated i.p. administration of paclitaxel or vincristine in rats. Nociceptive threshold was determined by the paw pressure method and/or von Frey test in the hindpaw. Tissue protein levels were determined by immunoblotting. Repeated i.p. administration of the anti-HMGB1-neutralizing antibody or recombinant human soluble thrombomodulin (rhsTM), known to inactivate HMGB1, prevented the development of hyperalgesia and/or allodynia induced by paclitaxel or vincristine in rats. A single i.p. or intraplantar (i.pl.) administration of the antibody or rhsTM reversed the chemotherapy-induced neuropathy. A single i.pl. administration of a TLR4 antagonist or low molecular weight heparin, known to inhibit RAGE, attenuated the hyperalgesia caused by i.pl. HMGB1 and also the chemotherapy-induced painful neuropathy. Paclitaxel or vincristine treatment significantly decreased protein levels of HMGB1 in the dorsal root ganglia, but not sciatic nerves. HMGB1 thus participates in both development and maintenance of chemotherapy-induced painful neuropathy, in part through RAGE and TLR4. HMGB1 inactivation is considered useful to prevent and treat the chemotherapy-induced painful neuropathy., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Soleus H-reflex reveals down modulation with increased postural difficulty. Role of this posture-related reflex modulation is thought to shift movement control toward higher motor centers in order to facilitate more precise postural control. Present study hypothesized that the ability to modulate H-reflex is related to one's ability to dynamically balance while in an unstable posture. This study examined the relationship between dynamic balancing ability and soleus H-reflex posture-related modulation. Thirty healthy adults participated. The soleus maximal H-reflex (Hmax), motor response (Mmax), and background EMG activity (bEMG) were obtained during three postural conditions: prone, open-legged standing, and closed-legged standing. Hmax/Mmax ratios were normalized via the corresponding bEMG in order to remove the effects of background muscle activity from the obtained H-reflex. Reflex modulation was calculated as the ratio of the normalized Hmax/Mmax ratios in one postural condition to another posture in a more difficult condition. Dynamic balancing ability was assessed by testing stability while standing on a wobble board. A significant negative correlation was observed between balancing scores and reflex modulation from open-legged standing to closed-legged standing. This suggests that the ability to modulate monosynaptic stretch reflex excitability in response to a changing posture is a significant factor for dynamic balancing., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Purpose: To study the long-term visual outcome of primary microtropia., Methods: A retrospective review was made on 31 patients with primary microtropia with the follow-up period of 5 years or more (5-15 years, mean=9.2 years) seen during 16 years from 1985 to 2000 at Okayama University Hospital. The patients were 16 boys and 15 girls, with the age at the initial visit ranging from 5 to 16 years (mean=9.3 years)., Results: All patients showed anomalous retinal correspondence, peripheral fusion, 10 prism diopters or smaller esodeviation at the initial and final visit. At the initial visit, TNO stereoacuity was absent in 24 patients, 480 seconds in 3, and 240 seconds in 4. The visual acuity was 0.8 or better in both eyes of 16 patients, but 0.7 or worse in 1 eye or both eyes of 15 patients. At the final visit, the 24 patients with the absence of stereoacuity still showed its absence, while stereoacuity remained unchanged or improved in the 7 patients with initial stereoacuity of 480 seconds or better. In the 15 patients with 0.7 or worse visual acuity, it improved to 0.8 or better in 7 patients while it remained 0.7 or worse in the other 8 patients. Poor visual acuity had no relation to the absence of TNO stereoacuity at the initial and final visits., Conclusion: Patients with primary microtropia could be largely classified into those with the absence of TNO stereoacuity throughout the course of treatment and those with some levels of stereoacuity that had a chance to improve during the follow-up.