Medial plantar nerve ligation as a novel model of neuropathic pain in mice: pharmacological and molecular characterization.

Morena B Sant’Anna,Sergio H Ferreira,José C Alves-Filho,Tiago A Bozzo,Thiago M Cunha,Fernando Q Cunha,Ricardo Kusuda,Guilherme R Souza,Gabriel S Bassi

doi:10.1038/srep26955

Morena B Sant’Anna, Sergio H Ferreira + Show 7 more

Open Access

https://doi.org/10.1038/srep26955

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Journal: Scientific reports	Publication Date: May 27, 2016
Citations: 18	License type: CC BY 4.0

Affiliation: Universidade de São Paulo

Abstract

Peripheral neuropathic pain is a consequence of an injury/disease of the peripheral nerves. The mechanisms involved in its pathophysiology are not entirely understood. To better understand the mechanisms involved in the development of peripheral nerve injury-induced neuropathic pain, more experimental models are required. Here, we developed a novel peripheral neuropathic pain model in mice by using a minimally invasive surgery and medial plantar nerve ligation (MPNL). After MPNL, mechanical allodynia was established, and mice quickly recovered from the surgery without any significant motor impairment. MPNL causes an increased expression of ATF-3 in the sensory neurons. At 14 days after surgery, gabapentin was capable of reversing the mechanical allodynia, whereas anti-inflammatory drugs and opioids were ineffective. MPNL-induced neuropathic pain was mediated by glial cells activation and the production of TNF-α and IL-6 in the spinal cord. These results indicate MPNL as a reasonable animal model for the study of peripheral neuropathic pain, presenting analgesic pharmacological predictivity to clinically used drugs. The results also showed molecular phenotypic changes similar to other peripheral neuropathic pain models, with the advantage of a lack of motor impairment. These features indicate that MPNL might be more appropriate for the study of neuropathic pain than classical models.

Highlights

We propose a novel model to study peripheral neuropathic pain that is based on a minimal invasive surgery and medial plantar nerve ligation (MPNL) in mice (Fig. 1)
On the first day following the surgical procedure, the MPNL group showed a marked mechanical allodynia ipsilateral to the nerve injury, which was marginally different from sham-operated animals (Fig. 2A)
MPNL-induced mechanical allodynia persisted, at least, twenty-five days after surgery, whereas the nociceptive threshold of sham-operated animals recovered to control levels (P < 0.001, n = 5; Fig. 2)

Summary

Introduction

We propose a novel model to study peripheral neuropathic pain that is based on a minimal invasive surgery and medial plantar nerve ligation (MPNL) in mice (Fig. 1). The pharmacological predictivity and molecular mechanisms involved in MPNL-induced peripheral neuropathic pain were addressed. On the first day following the surgical procedure, the MPNL group showed a marked mechanical allodynia ipsilateral to the nerve injury, which was marginally different from sham-operated animals (Fig. 2A).

Results

Conclusion