Botulinum toxin type A and gabapentin attenuate postoperative pain and NK1 receptor internalization in rats

Xueyang Li, Ruijuan Guo, Yuqing Sun, Huili Li, Danxu Ma, Chen Zhang, Yun Guan, Junfa Li, Yun Wang

Research output: Contribution to journalArticle

Abstract

Treatment of postoperative pain remains a challenge in clinic. Botulinum toxin type A (BoNT/A) and gabapentin regulate the release of neurotransmitters from primary afferent neurons, but their effects of on postoperative pain are not clear. In the current study, using pain behavioral tests, Western blot analysis, and immunocytochemistry, we examined whether BoNT/A, alone or in combination with intrathecal gabapentin, inhibited pain hypersensitivity and attenuated the increase in neurokinin 1 (NK1) receptor internalization in dorsal horn neurons after plantar incision. Our data showed that pretreatment of rats with an intraplantar (2 U) 24 h before plantar incision or intrathecal (0.5 U) injection of BoNT/A 48 h before plantar incision induced a prolonged (3–5 days) decrease in pain scores and mechanical hypersensitivity, as compared to those observed with saline pretreatment. Both intraplantar and intrathecal BoNT/A pretreatment reduced synaptosomal-associated protein 25 levels in the ipsilateral lumbar dorsal root ganglia and spinal cord dorsal horn, and attenuated the increase in NK1 receptor internalization in dorsal horn neurons. Intrathecal administration of a sub-effective dose of gabapentin (50 μg) with BoNT/A (0.5 U) induced greater inhibition of pain hypersensitivity and NK1 receptor internalization than BoNT/A alone. These findings suggest that pretreatment with BoNT/A, alone or in combination with intrathecal gabapentin, may present a promising multimodal analgesia regimen for postoperative pain treatment.

Original languageEnglish (US)
Pages (from-to)52-62
Number of pages11
JournalNeurochemistry International
Volume116
DOIs
StatePublished - Jun 1 2018

Fingerprint

Neurokinin-1 Receptors
Type A Botulinum Toxins
Postoperative Pain
Posterior Horn Cells
Pain
Hypersensitivity
Synaptosomal-Associated Protein 25
Afferent Neurons
Spinal Ganglia
gabapentin
Analgesia
Neurotransmitter Agents
Western Blotting
Immunohistochemistry
Injections
Therapeutics

Keywords

  • Botulinum toxin type A
  • Gabapentin
  • Postoperative pain
  • Rats
  • Substance P

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

Botulinum toxin type A and gabapentin attenuate postoperative pain and NK1 receptor internalization in rats. / Li, Xueyang; Guo, Ruijuan; Sun, Yuqing; Li, Huili; Ma, Danxu; Zhang, Chen; Guan, Yun; Li, Junfa; Wang, Yun.

In: Neurochemistry International, Vol. 116, 01.06.2018, p. 52-62.

Research output: Contribution to journalArticle

Li, Xueyang ; Guo, Ruijuan ; Sun, Yuqing ; Li, Huili ; Ma, Danxu ; Zhang, Chen ; Guan, Yun ; Li, Junfa ; Wang, Yun. / Botulinum toxin type A and gabapentin attenuate postoperative pain and NK1 receptor internalization in rats. In: Neurochemistry International. 2018 ; Vol. 116. pp. 52-62.
@article{74324e38dd6742aea4f8e80672462b1c,
title = "Botulinum toxin type A and gabapentin attenuate postoperative pain and NK1 receptor internalization in rats",
abstract = "Treatment of postoperative pain remains a challenge in clinic. Botulinum toxin type A (BoNT/A) and gabapentin regulate the release of neurotransmitters from primary afferent neurons, but their effects of on postoperative pain are not clear. In the current study, using pain behavioral tests, Western blot analysis, and immunocytochemistry, we examined whether BoNT/A, alone or in combination with intrathecal gabapentin, inhibited pain hypersensitivity and attenuated the increase in neurokinin 1 (NK1) receptor internalization in dorsal horn neurons after plantar incision. Our data showed that pretreatment of rats with an intraplantar (2 U) 24 h before plantar incision or intrathecal (0.5 U) injection of BoNT/A 48 h before plantar incision induced a prolonged (3–5 days) decrease in pain scores and mechanical hypersensitivity, as compared to those observed with saline pretreatment. Both intraplantar and intrathecal BoNT/A pretreatment reduced synaptosomal-associated protein 25 levels in the ipsilateral lumbar dorsal root ganglia and spinal cord dorsal horn, and attenuated the increase in NK1 receptor internalization in dorsal horn neurons. Intrathecal administration of a sub-effective dose of gabapentin (50 μg) with BoNT/A (0.5 U) induced greater inhibition of pain hypersensitivity and NK1 receptor internalization than BoNT/A alone. These findings suggest that pretreatment with BoNT/A, alone or in combination with intrathecal gabapentin, may present a promising multimodal analgesia regimen for postoperative pain treatment.",
keywords = "Botulinum toxin type A, Gabapentin, Postoperative pain, Rats, Substance P",
author = "Xueyang Li and Ruijuan Guo and Yuqing Sun and Huili Li and Danxu Ma and Chen Zhang and Yun Guan and Junfa Li and Yun Wang",
year = "2018",
month = "6",
day = "1",
doi = "10.1016/j.neuint.2018.03.010",
language = "English (US)",
volume = "116",
pages = "52--62",
journal = "Neurochemistry International",
issn = "0197-0186",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Botulinum toxin type A and gabapentin attenuate postoperative pain and NK1 receptor internalization in rats

AU - Li, Xueyang

AU - Guo, Ruijuan

AU - Sun, Yuqing

AU - Li, Huili

AU - Ma, Danxu

AU - Zhang, Chen

AU - Guan, Yun

AU - Li, Junfa

AU - Wang, Yun

PY - 2018/6/1

Y1 - 2018/6/1

N2 - Treatment of postoperative pain remains a challenge in clinic. Botulinum toxin type A (BoNT/A) and gabapentin regulate the release of neurotransmitters from primary afferent neurons, but their effects of on postoperative pain are not clear. In the current study, using pain behavioral tests, Western blot analysis, and immunocytochemistry, we examined whether BoNT/A, alone or in combination with intrathecal gabapentin, inhibited pain hypersensitivity and attenuated the increase in neurokinin 1 (NK1) receptor internalization in dorsal horn neurons after plantar incision. Our data showed that pretreatment of rats with an intraplantar (2 U) 24 h before plantar incision or intrathecal (0.5 U) injection of BoNT/A 48 h before plantar incision induced a prolonged (3–5 days) decrease in pain scores and mechanical hypersensitivity, as compared to those observed with saline pretreatment. Both intraplantar and intrathecal BoNT/A pretreatment reduced synaptosomal-associated protein 25 levels in the ipsilateral lumbar dorsal root ganglia and spinal cord dorsal horn, and attenuated the increase in NK1 receptor internalization in dorsal horn neurons. Intrathecal administration of a sub-effective dose of gabapentin (50 μg) with BoNT/A (0.5 U) induced greater inhibition of pain hypersensitivity and NK1 receptor internalization than BoNT/A alone. These findings suggest that pretreatment with BoNT/A, alone or in combination with intrathecal gabapentin, may present a promising multimodal analgesia regimen for postoperative pain treatment.

AB - Treatment of postoperative pain remains a challenge in clinic. Botulinum toxin type A (BoNT/A) and gabapentin regulate the release of neurotransmitters from primary afferent neurons, but their effects of on postoperative pain are not clear. In the current study, using pain behavioral tests, Western blot analysis, and immunocytochemistry, we examined whether BoNT/A, alone or in combination with intrathecal gabapentin, inhibited pain hypersensitivity and attenuated the increase in neurokinin 1 (NK1) receptor internalization in dorsal horn neurons after plantar incision. Our data showed that pretreatment of rats with an intraplantar (2 U) 24 h before plantar incision or intrathecal (0.5 U) injection of BoNT/A 48 h before plantar incision induced a prolonged (3–5 days) decrease in pain scores and mechanical hypersensitivity, as compared to those observed with saline pretreatment. Both intraplantar and intrathecal BoNT/A pretreatment reduced synaptosomal-associated protein 25 levels in the ipsilateral lumbar dorsal root ganglia and spinal cord dorsal horn, and attenuated the increase in NK1 receptor internalization in dorsal horn neurons. Intrathecal administration of a sub-effective dose of gabapentin (50 μg) with BoNT/A (0.5 U) induced greater inhibition of pain hypersensitivity and NK1 receptor internalization than BoNT/A alone. These findings suggest that pretreatment with BoNT/A, alone or in combination with intrathecal gabapentin, may present a promising multimodal analgesia regimen for postoperative pain treatment.

KW - Botulinum toxin type A

KW - Gabapentin

KW - Postoperative pain

KW - Rats

KW - Substance P

UR - http://www.scopus.com/inward/record.url?scp=85044766713&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85044766713&partnerID=8YFLogxK

U2 - 10.1016/j.neuint.2018.03.010

DO - 10.1016/j.neuint.2018.03.010

M3 - Article

C2 - 29572051

AN - SCOPUS:85044766713

VL - 116

SP - 52

EP - 62

JO - Neurochemistry International

JF - Neurochemistry International

SN - 0197-0186

ER -