Remodelling of spinal nociceptive mechanisms in an animal model of monoarthritis

Reza Sharif Naeini,Henri A Ménard,James L Henry,Catherine M Cahill,Alfredo Ribeiro‐Da‐Silva

doi:10.1111/j.1460-9568.2005.04382.x

Abstract

Intra-articularly injected complete Freund's adjuvant creates in rats a chronic monoarthritis suitable for studying neuronal plasticity and chronic pain. Using such a model, we report electrophysiological and morphological evidence of alterations in somatosensory synaptic function. In arthritic rats, the baseline activity of dorsal spinal cord wide dynamic range or nociceptive-specific neurons was greater than in control animals. Moreover, neuronal responses elicited by an innocuous stimulation with von Frey filaments applied to the arthritic joint were greater in amplitude and produced the afterdischarge that normally characterizes a nociceptive response. In contrast to the response in control animals, passive movement of the arthritic joint produced an increase in the amplitude of the response of these neurons to iontophoretic application of glutamate receptor agonists over a time frame of 10-30 min. This potentiation was blocked by pretreatment with a neurokinin-1 (NK-1) receptor antagonist, suggesting the involvement of substance P. Ultrastructural analysis of the dorsal horn revealed that movement of the arthritic joint also induced NK-1 receptor internalization, indicative of nociception. Morphological examination revealed significantly increased expression of substance P and its receptor within the superficial dorsal horn of monoarthritic animals. These unique functional and chemical changes reflect alterations in both presynaptic and postsynaptic mechanisms in nociceptive transmission at the spinal level. Thus, although treatment of arthritis should obviously target its peripheral aetiology, targeting its central components is a logical therapeutic complementary objective.

Highlights

Pain is an important protective mechanism to minimize tissue damage; chronic pain lacks this teleological advantage and poses a burden to a significant proportion of the population
There was a significant increase in the circumference of the ipsilateral ankle immediately after complete Freund’s adjuvant (CFA) injection (Fig. 1A) and it persisted throughout the 21-day period of experimentation
Monoarthritic animals demonstrated a significant loss of ankle flexibility as well as a significant increase in vascular permeability throughout the time-course of experimentation

Summary

Introduction

Pain is an important protective mechanism to minimize tissue damage; chronic pain lacks this teleological advantage and poses a burden to a significant proportion of the population. Inflammatory pain mechanisms are a feature of a variety of chronic pain states including arthritis, back pain and temporomandibular joint disorder. Under conditions of chronic inflammatory pain, normally innocuous sensory stimuli are often perceived as painful (allodynia), and mild noxious sensory stimuli perceived as deeply painful (hyperalgesia). Both hyperalgesia and allodynia are thought to arise from sensitization of peripheral nociceptors (peripheral sensitization) and spinal dorsal horn neurons (central sensitization; Treede et al, 1992). Peripheral sensitization corresponds to a sustained activity of primary afferent fibres and features an increase in the efficacy of synaptic transmission between primary afferent fibres and dorsal horn neurons (Woolf & Salter, 2000).

Methods

Results

Conclusion