Orexin-A modulates glutamatergic NMDA-dependent spinal reflex potentiation via inhibition of NR2B subunit

Hsien Yu Peng, Hung Ming Chang, Sarah Y. Chang, Kwong Chung Tung, Shin Da Lee, Dylan Chou, Cheng Yuan Lai, Chun Hsien Chiu, Gin Den Chen, Tzer Bin Lin

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Glucose-sensitive neurons in the lateral hypothalamic area produce orexin-A (OxA) as well as orexin-B (OxB) and send their axons to the spinal dorsal horn, which predominantly expresses orexin receptor-1 (OX-1), showing a higher sensitivity to OxA. The purpose of the present study was to assess the effects of OxA on the induction of a novel form of activity-dependent reflex potentiation, spinal reflex potentiation (SRP), in the pelvicurethral reflex activity. External urethra sphincter electromyogram in response to pelvic afferent nerve test stimulation (TS; 1/30 Hz) or repetitive stimulation (RS; 1 Hz) was recorded in anesthetized rats. TS evoked a baseline reflex activity, whereas RS produced SRP, which was abolished by intrathecal OxA (30 nM, 10 μl). Intrathecal SB-408124 (10 μM, 10 μl), an OX-1 antagonist, reversed the abolition on SRP caused by OxA. Although there is, so far, no NR2A- and NR2B-specific agonist available, N-methyl-D-aspartate (NMDA) reversed the abolition on the RS-induced SRP caused by the co-administration of OxA and Co-101244 (30 nM, 10 μl; an NMDA NR2B subunit antagonist), but it did not reverse the abolition by the co-administration of OxA and PPPA (300 nM, 10 μl; an NMDA NR2A subunit antagonist). In conclusion, the activation of descending orexinergic fibers may inhibit the repetitive afferent input-induced central sensitization of pelvic-urethral reflex activity and urethra hyperactivity, indicating that spinal orexinergic neural transmission may be a novel target for the treatment of patients with neuropathetic or postinflammatory pain of pelvic origin.

Original languageEnglish
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume295
Issue number1
DOIs
Publication statusPublished - Jul 2008
Externally publishedYes

Fingerprint

N-Methylaspartate
Reflex
Orexin Receptors
Urethra
Lateral Hypothalamic Area
Central Nervous System Sensitization
Pelvic Pain
Orexins
Inhibition (Psychology)
Electromyography
Synaptic Transmission
Neurons
Axons
Rats
Chemical activation
Glucose
Fibers

Keywords

  • Pelvic nerve
  • Rats
  • Spinal cord
  • Urethra

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Biochemistry

Cite this

Orexin-A modulates glutamatergic NMDA-dependent spinal reflex potentiation via inhibition of NR2B subunit. / Peng, Hsien Yu; Chang, Hung Ming; Chang, Sarah Y.; Tung, Kwong Chung; Lee, Shin Da; Chou, Dylan; Lai, Cheng Yuan; Chiu, Chun Hsien; Chen, Gin Den; Lin, Tzer Bin.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 295, No. 1, 07.2008.

Research output: Contribution to journalArticle

Peng, Hsien Yu ; Chang, Hung Ming ; Chang, Sarah Y. ; Tung, Kwong Chung ; Lee, Shin Da ; Chou, Dylan ; Lai, Cheng Yuan ; Chiu, Chun Hsien ; Chen, Gin Den ; Lin, Tzer Bin. / Orexin-A modulates glutamatergic NMDA-dependent spinal reflex potentiation via inhibition of NR2B subunit. In: American Journal of Physiology - Endocrinology and Metabolism. 2008 ; Vol. 295, No. 1.
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AU - Lee, Shin Da

AU - Chou, Dylan

AU - Lai, Cheng Yuan

AU - Chiu, Chun Hsien

AU - Chen, Gin Den

AU - Lin, Tzer Bin

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AB - Glucose-sensitive neurons in the lateral hypothalamic area produce orexin-A (OxA) as well as orexin-B (OxB) and send their axons to the spinal dorsal horn, which predominantly expresses orexin receptor-1 (OX-1), showing a higher sensitivity to OxA. The purpose of the present study was to assess the effects of OxA on the induction of a novel form of activity-dependent reflex potentiation, spinal reflex potentiation (SRP), in the pelvicurethral reflex activity. External urethra sphincter electromyogram in response to pelvic afferent nerve test stimulation (TS; 1/30 Hz) or repetitive stimulation (RS; 1 Hz) was recorded in anesthetized rats. TS evoked a baseline reflex activity, whereas RS produced SRP, which was abolished by intrathecal OxA (30 nM, 10 μl). Intrathecal SB-408124 (10 μM, 10 μl), an OX-1 antagonist, reversed the abolition on SRP caused by OxA. Although there is, so far, no NR2A- and NR2B-specific agonist available, N-methyl-D-aspartate (NMDA) reversed the abolition on the RS-induced SRP caused by the co-administration of OxA and Co-101244 (30 nM, 10 μl; an NMDA NR2B subunit antagonist), but it did not reverse the abolition by the co-administration of OxA and PPPA (300 nM, 10 μl; an NMDA NR2A subunit antagonist). In conclusion, the activation of descending orexinergic fibers may inhibit the repetitive afferent input-induced central sensitization of pelvic-urethral reflex activity and urethra hyperactivity, indicating that spinal orexinergic neural transmission may be a novel target for the treatment of patients with neuropathetic or postinflammatory pain of pelvic origin.

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