The effect of recombinant botulinum neurotoxin A on neuropathic pain in the spared nerve injury mouse model

Rasmus E. Hammer; Akinyemi A. Omoniyi; Mette Richner; Stephane Lezmi; Christian B. Vaegter; Mikhail Kalinichev; Pall Karlsson; Jens R. Nyengaard

doi:10.1007/s00702-025-02978-0

The effect of recombinant botulinum neurotoxin A on neuropathic pain in the spared nerve injury mouse model

Rasmus E. Hammer
, Akinyemi A. Omoniyi
, Mette Richner
, Stephane Lezmi
, Christian B. Vaegter
, Mikhail Kalinichev^*
, Pall Karlsson
, Jens R. Nyengaard

^*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

Abstract

Neuropathic pain following traumatic nerve injury is a disabling chronic pain disorder characterized by sensory abnormalities such as mechanical allodynia. Botulinum neurotoxin type A (BoNT/A) has shown analgesic properties in a range of clinical pain conditions and in animal models. Here, we investigated analgesic efficacy of recombinant BoNT/A1 (rBoNT/A1; IPN10260) in the spared nerve injury (SNI) mouse model of neuropathic pain. Potential tissue site and mechanisms of action were explored by analyzing a series of pain biomarkers in the ipsilateral dorsal root ganglion (DRG) and the spinal cord. C57Bl6 mice received either SNI- or a sham surgery 14 days before being treated with either rBoNT/A1 or vehicle. Mechanical sensitivity was evaluated in von Frey tests performed at baseline and throughout the experiment. DRGs and spinal cords were collected for quantitative microscopy of immunohistochemically labelled pain-related targets. rBoNT/A1-injection resulted in significant and prolonged (up to 14 days) increases in mechanical threshold compared to vehicle in SNI-operated mice. Volume of type B DRG neurons and number density of Iba1-positive cells in DRG were significantly increased in the SNI-operated animals in comparison to the sham-operated controls, however no significant effect of rBoNT/A1 could be demonstrated. Among spinal cord biomarkers, no effects were observed. These results demonstrate that rBoNT/A1 reduces mechanical allodynia following peripheral nerve injury, but the mechanisms remain elusive. Investigating these biomarkers in a challenged system (diabetes, chemotherapy, etc.) might extend the window of activation, possibly better exposing analgesic mechanisms of rBoNT/A1.

Original language	English
Journal	Journal of Neural Transmission
Volume	132
Pages (from-to)	1779–1795
Number of pages	17
ISSN	0300-9564
DOIs	https://doi.org/10.1007/s00702-025-02978-0
Publication status	Published - Aug 2025

Keywords

Analgesia
Animal model
Antinociceptive efficacy
Chronic pain
von Frey

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@article{76110fe3788e43cbb78af6009795e282,

title = "The effect of recombinant botulinum neurotoxin A on neuropathic pain in the spared nerve injury mouse model",

abstract = "Neuropathic pain following traumatic nerve injury is a disabling chronic pain disorder characterized by sensory abnormalities such as mechanical allodynia. Botulinum neurotoxin type A (BoNT/A) has shown analgesic properties in a range of clinical pain conditions and in animal models. Here, we investigated analgesic efficacy of recombinant BoNT/A1 (rBoNT/A1; IPN10260) in the spared nerve injury (SNI) mouse model of neuropathic pain. Potential tissue site and mechanisms of action were explored by analyzing a series of pain biomarkers in the ipsilateral dorsal root ganglion (DRG) and the spinal cord. C57Bl6 mice received either SNI- or a sham surgery 14 days before being treated with either rBoNT/A1 or vehicle. Mechanical sensitivity was evaluated in von Frey tests performed at baseline and throughout the experiment. DRGs and spinal cords were collected for quantitative microscopy of immunohistochemically labelled pain-related targets. rBoNT/A1-injection resulted in significant and prolonged (up to 14 days) increases in mechanical threshold compared to vehicle in SNI-operated mice. Volume of type B DRG neurons and number density of Iba1-positive cells in DRG were significantly increased in the SNI-operated animals in comparison to the sham-operated controls, however no significant effect of rBoNT/A1 could be demonstrated. Among spinal cord biomarkers, no effects were observed. These results demonstrate that rBoNT/A1 reduces mechanical allodynia following peripheral nerve injury, but the mechanisms remain elusive. Investigating these biomarkers in a challenged system (diabetes, chemotherapy, etc.) might extend the window of activation, possibly better exposing analgesic mechanisms of rBoNT/A1.",

keywords = "Analgesia, Animal model, Antinociceptive efficacy, Chronic pain, von Frey",

author = "\{E. Hammer\}, Rasmus and \{A. Omoniyi\}, Akinyemi and Mette Richner and Stephane Lezmi and \{B. Vaegter\}, Christian and Mikhail Kalinichev and Pall Karlsson and \{R. Nyengaard\}, Jens",

year = "2025",

month = aug,

doi = "10.1007/s00702-025-02978-0",

language = "English",

volume = "132",

pages = "1779–1795",

journal = "Journal of Neural Transmission",

issn = "0300-9564",

publisher = "Springer",

}

The effect of recombinant botulinum neurotoxin A on neuropathic pain in the spared nerve injury mouse model. / E. Hammer, Rasmus; A. Omoniyi, Akinyemi; Richner, Mette et al.
In: Journal of Neural Transmission, Vol. 132, 08.2025, p. 1779–1795.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - The effect of recombinant botulinum neurotoxin A on neuropathic pain in the spared nerve injury mouse model

AU - E. Hammer, Rasmus

AU - A. Omoniyi, Akinyemi

AU - Richner, Mette

AU - Lezmi, Stephane

AU - B. Vaegter, Christian

AU - Kalinichev, Mikhail

AU - Karlsson, Pall

AU - R. Nyengaard, Jens

PY - 2025/8

Y1 - 2025/8

N2 - Neuropathic pain following traumatic nerve injury is a disabling chronic pain disorder characterized by sensory abnormalities such as mechanical allodynia. Botulinum neurotoxin type A (BoNT/A) has shown analgesic properties in a range of clinical pain conditions and in animal models. Here, we investigated analgesic efficacy of recombinant BoNT/A1 (rBoNT/A1; IPN10260) in the spared nerve injury (SNI) mouse model of neuropathic pain. Potential tissue site and mechanisms of action were explored by analyzing a series of pain biomarkers in the ipsilateral dorsal root ganglion (DRG) and the spinal cord. C57Bl6 mice received either SNI- or a sham surgery 14 days before being treated with either rBoNT/A1 or vehicle. Mechanical sensitivity was evaluated in von Frey tests performed at baseline and throughout the experiment. DRGs and spinal cords were collected for quantitative microscopy of immunohistochemically labelled pain-related targets. rBoNT/A1-injection resulted in significant and prolonged (up to 14 days) increases in mechanical threshold compared to vehicle in SNI-operated mice. Volume of type B DRG neurons and number density of Iba1-positive cells in DRG were significantly increased in the SNI-operated animals in comparison to the sham-operated controls, however no significant effect of rBoNT/A1 could be demonstrated. Among spinal cord biomarkers, no effects were observed. These results demonstrate that rBoNT/A1 reduces mechanical allodynia following peripheral nerve injury, but the mechanisms remain elusive. Investigating these biomarkers in a challenged system (diabetes, chemotherapy, etc.) might extend the window of activation, possibly better exposing analgesic mechanisms of rBoNT/A1.

AB - Neuropathic pain following traumatic nerve injury is a disabling chronic pain disorder characterized by sensory abnormalities such as mechanical allodynia. Botulinum neurotoxin type A (BoNT/A) has shown analgesic properties in a range of clinical pain conditions and in animal models. Here, we investigated analgesic efficacy of recombinant BoNT/A1 (rBoNT/A1; IPN10260) in the spared nerve injury (SNI) mouse model of neuropathic pain. Potential tissue site and mechanisms of action were explored by analyzing a series of pain biomarkers in the ipsilateral dorsal root ganglion (DRG) and the spinal cord. C57Bl6 mice received either SNI- or a sham surgery 14 days before being treated with either rBoNT/A1 or vehicle. Mechanical sensitivity was evaluated in von Frey tests performed at baseline and throughout the experiment. DRGs and spinal cords were collected for quantitative microscopy of immunohistochemically labelled pain-related targets. rBoNT/A1-injection resulted in significant and prolonged (up to 14 days) increases in mechanical threshold compared to vehicle in SNI-operated mice. Volume of type B DRG neurons and number density of Iba1-positive cells in DRG were significantly increased in the SNI-operated animals in comparison to the sham-operated controls, however no significant effect of rBoNT/A1 could be demonstrated. Among spinal cord biomarkers, no effects were observed. These results demonstrate that rBoNT/A1 reduces mechanical allodynia following peripheral nerve injury, but the mechanisms remain elusive. Investigating these biomarkers in a challenged system (diabetes, chemotherapy, etc.) might extend the window of activation, possibly better exposing analgesic mechanisms of rBoNT/A1.

KW - Analgesia

KW - Animal model

KW - Antinociceptive efficacy

KW - Chronic pain

KW - von Frey

UR - https://www.scopus.com/pages/publications/105014779454

U2 - 10.1007/s00702-025-02978-0

DO - 10.1007/s00702-025-02978-0

M3 - Journal article

C2 - 40886229

AN - SCOPUS:105014779454

SN - 0300-9564

VL - 132

SP - 1779

EP - 1795

JO - Journal of Neural Transmission

JF - Journal of Neural Transmission

ER -

The effect of recombinant botulinum neurotoxin A on neuropathic pain in the spared nerve injury mouse model

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Keywords

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