Elsevier

Neuroscience Research

Volume 70, Issue 3, July 2011, Pages 285-293
Neuroscience Research

Painful muscle stimulation preferentially activates emotion-related brain regions compared to painful skin stimulation

https://doi.org/10.1016/j.neures.2011.04.001Get rights and content

Abstract

Skin pain and muscle pain are categorically distinct from each other. While skin pain is a sharp, spatially localized sensation, muscle pain is a dull, poorly localized and more unpleasant one. We hypothesized that there are specific brain regions preferentially activated by muscle pain compared to skin pain. To test this hypothesis, brain responses were recorded from 13 normal male subjects in response to repeated painful electrical stimulation of the muscle and skin of the left leg, using 3-T magnetic resonance imaging scanner. The common brain regions that responded to painful stimulations of both skin and muscle were the thalamus, anterior cingulate cortex, bilateral insula, contralateral primary and secondary somatosensory cortices, and ipsilateral cerebellum. Brain regions specifically activated by muscle stimulation were the midbrain, bilateral amygdala, caudate, orbitofrontal cortex, hippocampus, parahippocampus and superior temporal pole, most of which are related to emotion. Regions except the midbrain showed contralateral preference. These results suggest that dull sensation, which is characteristic of muscular pain, is related with processing in these brain regions.

Highlights

► Painful skin stimulation evoked activation in SI, SII, insula and ACC, as expected. ► Several brain regions were preferentially activated by painful muscle stimulation. ► The regions included the midbrain, bilateral amygdala and orbitofrontal cortex. ► The parahippocampus and superior temporal pole were also activated by muscle pain.

Introduction

Muscle pain, such as shoulder pain and low back pain, are common clinical problems which impair the quality of patient's life. Although actual prevalence of musculoskeletal pain is not clear, it is suggested that such pain is common not only among adults, but also among the adolescent population (McBeth and Jones, 2007). In Japan, 21.4 million people, which is 24.3% of the population aged 30 years or older, were estimated to have low back pain in 2005 (Suka and Yoshida, 2009), and 9.1 million (9% of the total population) were estimated to have musculoskeletal pain that interferes with daily life (Suka and Yoshida, 2005). As often discussed, skin pain and muscle pain are categorically distinct from each other (Henderson et al., 2006, Kupers et al., 2004, Niddam et al., 2002, Schreckenberger et al., 2005, Svensson et al., 1997a): While skin pain is often described as sharp and spatially localized sensation, muscle pain is usually dull, poorly localized and more unpleasant than cutaneous pain (Ikemoto et al., 2006). These distinct characteristics easily lead us to hypothesize that corresponding brain activities should be in some respect different between muscle and skin pain.

Earlier studies on the central mechanism of pain have predominantly dealt with skin pain using contact thermode (Peyron et al., 2000). Against this background, several researchers have laid stress upon the necessity of studies on the central mechanism of the muscle pain (Henderson et al., 2006, Kupers et al., 2004, Niddam et al., 2002, Schreckenberger et al., 2005, Svensson et al., 1997b). Although little difference has been reported between the brain activity responsible for muscle pain and that for skin pain in earlier studies (Svensson et al., 1997b), recent studies are revealing such differences. Niddam et al. (2002) and Schreckenberger et al. (2005), for example, have reported increased neural activities in response to painful muscle stimulation at inferior/middle frontal gyrus, with electric stimulation and with acidic buffer injection, respectively. Activity at the caudate nucleus, a part of the basal ganglia known to be implicated in motor functions, has been also reported (Kupers et al., 2004, Niddam et al., 2002). Kupers et al. (2004) compared brain activities induced by hypertonic saline injection to the muscle with those induced by tactile stimulation of the skin with a von Frey hair. Furthermore, Henderson et al. (2006) showed muscle specific response at the ipsilateral anterior insula using hypertonic saline injection. In addition, they found that activity in the perigenual cingulate cortex, which is implicated in emotional response, was significantly decreased in muscle pain than in cutaneous pain. Other brain regions that are associated with aversive emotion include hippocampus (Viveros et al., 2007), amygdala (Fanselow and Gale, 2003), midbrain (Brandao et al., 2003) and orbitofrontal cortex (Rolls, 2000). So far, brain regions responsible for the dull sensation, which is the special characteristic of the muscle pain compared to the skin pain, are not clear.

In this study we used electrical stimulation of the skin and the muscle of the similar subjective intensity levels, and it was synchronized with fMRI scans so that the analysis is statistically more robust and accurately pinpoints finer differences between the respective brain regions responsible for painful muscle and skin stimulation. In addition ROI analysis was performed focused on the brain areas that are considered to be related to emotion.

Section snippets

Subjects

We studied 13 healthy male volunteers (aged 20–36 years, mean ± S.E.M.: 26 ± 1 years) with the approval of both the Ethical Committee for Human and Genome Research of Research Institute of Environmental Medicine, Nagoya University and the Ethical Committee of the National Institute for Physiological Sciences, Japan. Informed written consent was obtained from all subjects and the study adhered to the tenets of the Declaration of Helsinki.

Stimulus

Electrical stimulation was used to induce pain (electrical

Pain perception

Despite similar pain intensities, there were clear differences in the sensory descriptors ascribed to muscle versus skin pain. Subcutaneous electric current evoked pain that was localized to the skin immediately surrounding the needle insertion site. In contrast, intramuscular electric stimuli evoked a deep, dull and unpleasant sensation, that is spatially more diffuse compared to the case of the subcutaneous stimulation. Painful sensations induced by electrical stimulation of the skin or

Discussion

In addition to activation of areas that are well established as pain neuromatrices (Peyron et al., 2000) such as the primary and secondary somatosensory cortex, insula, anterior cingulate cortex and thalamus, we found that the midbrain, amygdala, caudate, orbitofrontal cortices, hippocampus, parahippocampus and superior temporal pole responded preferentially to painful muscle stimulation. Most of these areas are thought to be involved in emotion. Increased activities in response to painful

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