Experimental myofascial trigger point creation in rodents

Abstract

Myofascial pain syndrome is one of the most common forms of muscle pain. In this syndrome, pain is originated by the so-called trigger points, which consists of a set of palpable contraction knots in the muscle. It has been proposed that a high, spontaneous neurotransmission may be involved in the generation of these contraction knots. To confirm this hypothesis, we exposed mouse muscles to an anticholinesterasic agent to increase the neurotransmision in the synaptic cleft in two different conditions, in vivo and ex vivo experiments. Using intracellular recordings, a sharp increase in the spontaneous neurotransmission in the levator auris longus muscle and a lower increase in the diaphragm muscle could be seen. Likewise, electromyography recordings reveal an elevated endplate noise in gastrocnemius muscle of treated animals. These changes are associated with structural changes such as abundant neuromuscular contracted zones observed by rhodaminated α-bungarotoxin and the presence of abundant glycosaminoglycans around the contraction knots, as shown by Alcian PAS staining. In a second set of experiments, we aimed at demonstrating that the increases in the neurotransmission reproduced most of the clinical signs associated to a trigger point. We exposed rats to the anticholinesterase agent neostigmine, and 30 min afterward we observed the presence of palpable taut bands, the echocardiographic presence of contraction knots, and local twitch responses upon needle stimulation. In summary, we demonstrated that increased neurotransmission induced trigger points in both rats and mice, as evidenced by glycosaminoglycans around the contraction zones as a novel hallmark of this pathology. NEW & NOTEWORTHY In rodents, when neostigmine was injected subcutaneously, the neuromuscular neurotransmission increased, and several changes can be observed: an elevated endplate noise compared with normal endplate noise, as evidenced by electromyographyc recording; many muscular fibers with contraction knots (narrower sarcomeres and locally thickened muscle fiber) surrounded by infiltration of connective tissue like glycosaminoglycans molecules; and palpable taut bands and local twitch responses upon needle stimulation. Several of these signs are also observed in humans with muscle pain.

Effects of a Fat-Rich Diet on the Spontaneous Release of Acetylcholine in the Neuromuscular Junction of Mice

“…The muscle used for this study was the gastrocnemius because of its ease of access and suitability. Recordings were obtained with an electromyography system (MedelecMystro plus, GR20) using a monopolar EMG needle (Natus Manufacturing Limited, London, UK) [ 17 ]. The needle was slowly inserted into the muscle and once inside, it was moved in order to enable recording in all directions.…”

“…The needle was slowly inserted into the muscle and once inside, it was moved in order to enable recording in all directions. The muscle was divided into twelve areas to cover both the entire muscle and avoid recording the same endplate noise twice [ 17 ]. The recording needle was introduced into the gastrocnemius until an audible change was heard.…”

“…In 2005, Shah identified a high presence of several of these substances (pH, SP, IL-6, TNF-α, CGRP…) in the environment of MTrPs [ 16 ]. On the other hand, in our laboratory, we experimentally cause the appearance of contracted subsynaptic sarcomere by increasing local ACh with anticholinesterase drugs [ 17 ]. This increase in ACh release can be recorded by needle electromyography as spontaneous low-voltage electrical activity (30–60 mV) like endplate noise [ 14 , 17 , 18 ].…”

Percutaneous Application of Galvanic Current in Rodents Reverses Signs of Myofascial Trigger Points

“…An increase in ACh released spontaneously at the level of the motor endplate is directly related to the generation of myofascial trigger points (MTrPs) [1,4]. e increase in spontaneously released ACh may be recorded electromyographically via a characteristic recording known as endplate noise [5,6].…”

Inhibition of Peripheral ERK Signaling Ameliorates Persistent Muscle Pain Around Trigger Points in Rats

“…Recently, in the same model as that used in this study, inflammatory cytokine expression levels were significantly increased in the MTrPs of the model group 9 , and Huang and colleagues used this model to study proteomics, providing valuable clues for improved understanding of the pathogenesis of myofascial pain 10 . A sustained increase in acetylcholine in the synaptic cleft may play a key role in MTrP formation 11 .…”