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The antiallodynic effect of Neurotropin is mediated via activation of descending pain inhibitory systems in rats with spinal nerve ligation.
Anesth Analg. 2008 Sep; 107(3):1064-9.A&A

Abstract

BACKGROUND

Neurotropin, a nonprotein extract isolated from inflamed skin of rabbits inoculated with vaccinia virus, is widely used in Japan to treat chronic pain such as neuropathic pain. Although some studies have been conducted on the mechanism of the antiallodynic action of Neurotropin, this mechanism has yet to be adequately clarified.

METHODS

The left fifth lumbar nerve of rats was tightly ligated with silk sutures under pentobarbital anesthesia. Mechanical allodynia was confirmed by measuring the hindpaw withdrawal threshold in response to application of von Frey filaments. Behavioral tests were performed at 28 days after nerve ligation. Neurotropin was administered IV, intrathecally or intracerebroventricularly in L5 spinal nerve ligation (L5-SNL) rats. We examined the effects of noradrenergic, serotonergic and gamma-aminobutyric acid (GABA)ergic antagonists on the antiallodynic action of Neurotropin in L5-SNL rats. Yohimbine hydrochloride (yohimbine) was used as an alpha(2) adrenoceptor antagonist, ketanserin tartrate (ketanserin) as a 5-HT(2A) receptor antagonist, MDL72,222 as a 5-HT(3) receptor antagonist, (-)-bicuculline methobromide (bicuculline) as a GABA(A) receptor antagonist, and CGP35,348 as a GABA(B) receptor antagonist, and intrathecally injected.

RESULTS

IV (50-100 NU/kg) doses of Neurotropin elicited an antiallodynic action in L5-SNL rats. Moreover, intracerebroventricular (400 mNU/rat), but not intrathecal, injection of Neurotropin inhibited allodynia. The antiallodynic action of Neurotropin (100 NU/kg, IV) was antagonized by intrathecal injections of yohimbine (10 nmol/rat), ketanserin (30 nmol/rat), MDL72,222(30 nmol/rat), bicuculline (0.6 nmol/rat) and CGP35348 (30 nmol/rat). On the other hand, the antiallodynic action of intrathecally injected m-CPBG (5-HT(3) receptor agonist) was reversed by intrathecal injection of bicuculline and CGP35348, suggesting interaction of 5-HT(3) receptors and spinal inhibitory (GABAergic) interneurons.

CONCLUSIONS

These results suggest that the antiallodynic effect of Neurotropin is mediated via activation of descending pain inhibitory systems, such as the noradrenergic and serotonergic systems, which project from supraspinal sites to the spinal dorsal horn. In addition, activation of inhibitory GABAergic interneurons via 5-HT(3) receptors by serotonin released in the spinal dorsal horn may also be involved in the antiallodynic action of Neurotropin.

Authors+Show Affiliations

Department of Development Research, Institute of Bio-active Science, Nippon Zoki Pharmaceutical Co., Ltd., 442-1, Kinashi, Kato, Hyogo, 673-1461, Japan. r-okazaki@nippon-zoki.co.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18713930

Citation

Okazaki, Ryohei, et al. "The Antiallodynic Effect of Neurotropin Is Mediated Via Activation of Descending Pain Inhibitory Systems in Rats With Spinal Nerve Ligation." Anesthesia and Analgesia, vol. 107, no. 3, 2008, pp. 1064-9.
Okazaki R, Namba H, Yoshida H, et al. The antiallodynic effect of Neurotropin is mediated via activation of descending pain inhibitory systems in rats with spinal nerve ligation. Anesth Analg. 2008;107(3):1064-9.
Okazaki, R., Namba, H., Yoshida, H., Okai, H., Miura, T., & Kawamura, M. (2008). The antiallodynic effect of Neurotropin is mediated via activation of descending pain inhibitory systems in rats with spinal nerve ligation. Anesthesia and Analgesia, 107(3), 1064-9. https://doi.org/10.1213/ane.0b013e31817e7a59
Okazaki R, et al. The Antiallodynic Effect of Neurotropin Is Mediated Via Activation of Descending Pain Inhibitory Systems in Rats With Spinal Nerve Ligation. Anesth Analg. 2008;107(3):1064-9. PubMed PMID: 18713930.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The antiallodynic effect of Neurotropin is mediated via activation of descending pain inhibitory systems in rats with spinal nerve ligation. AU - Okazaki,Ryohei, AU - Namba,Hiroyoshi, AU - Yoshida,Hiroyuki, AU - Okai,Hisashi, AU - Miura,Tomoshi, AU - Kawamura,Minoru, PY - 2008/8/21/pubmed PY - 2008/9/13/medline PY - 2008/8/21/entrez SP - 1064 EP - 9 JF - Anesthesia and analgesia JO - Anesth Analg VL - 107 IS - 3 N2 - BACKGROUND: Neurotropin, a nonprotein extract isolated from inflamed skin of rabbits inoculated with vaccinia virus, is widely used in Japan to treat chronic pain such as neuropathic pain. Although some studies have been conducted on the mechanism of the antiallodynic action of Neurotropin, this mechanism has yet to be adequately clarified. METHODS: The left fifth lumbar nerve of rats was tightly ligated with silk sutures under pentobarbital anesthesia. Mechanical allodynia was confirmed by measuring the hindpaw withdrawal threshold in response to application of von Frey filaments. Behavioral tests were performed at 28 days after nerve ligation. Neurotropin was administered IV, intrathecally or intracerebroventricularly in L5 spinal nerve ligation (L5-SNL) rats. We examined the effects of noradrenergic, serotonergic and gamma-aminobutyric acid (GABA)ergic antagonists on the antiallodynic action of Neurotropin in L5-SNL rats. Yohimbine hydrochloride (yohimbine) was used as an alpha(2) adrenoceptor antagonist, ketanserin tartrate (ketanserin) as a 5-HT(2A) receptor antagonist, MDL72,222 as a 5-HT(3) receptor antagonist, (-)-bicuculline methobromide (bicuculline) as a GABA(A) receptor antagonist, and CGP35,348 as a GABA(B) receptor antagonist, and intrathecally injected. RESULTS: IV (50-100 NU/kg) doses of Neurotropin elicited an antiallodynic action in L5-SNL rats. Moreover, intracerebroventricular (400 mNU/rat), but not intrathecal, injection of Neurotropin inhibited allodynia. The antiallodynic action of Neurotropin (100 NU/kg, IV) was antagonized by intrathecal injections of yohimbine (10 nmol/rat), ketanserin (30 nmol/rat), MDL72,222(30 nmol/rat), bicuculline (0.6 nmol/rat) and CGP35348 (30 nmol/rat). On the other hand, the antiallodynic action of intrathecally injected m-CPBG (5-HT(3) receptor agonist) was reversed by intrathecal injection of bicuculline and CGP35348, suggesting interaction of 5-HT(3) receptors and spinal inhibitory (GABAergic) interneurons. CONCLUSIONS: These results suggest that the antiallodynic effect of Neurotropin is mediated via activation of descending pain inhibitory systems, such as the noradrenergic and serotonergic systems, which project from supraspinal sites to the spinal dorsal horn. In addition, activation of inhibitory GABAergic interneurons via 5-HT(3) receptors by serotonin released in the spinal dorsal horn may also be involved in the antiallodynic action of Neurotropin. SN - 1526-7598 UR - https://www.unboundmedicine.com/medline/citation/18713930/The_antiallodynic_effect_of_Neurotropin_is_mediated_via_activation_of_descending_pain_inhibitory_systems_in_rats_with_spinal_nerve_ligation_ L2 - https://doi.org/10.1213/ane.0b013e31817e7a59 DB - PRIME DP - Unbound Medicine ER -