Painful muscle stimulation preferentially activates emotion-related brain regions compared to painful skin stimulation
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
References (38)
- et al.
High opiate receptor binding potential in the human lateral pain system
Neuroimage
(2006) - et al.
The relevance of neuronal substrates of defense in the midbrain tectum to anxiety and stress: empirical and conceptual considerations
Eur. J. Pharmacol.
(2003) Anxiety and affective style: role of prefrontal cortex and amygdala
Biol. Psychiatry
(2002)A systematic review of neuroimaging data during visceral stimulation
Am. J. Gastroenterol.
(2003)- et al.
Event-related fMRI: characterizing differential responses
Neuroimage
(1998) - et al.
Classical and Bayesian inference in neuroimaging: theory
Neuroimage
(2002) - et al.
Distinct forebrain activity patterns during deep versus superficial pain
Pain
(2006) - et al.
Central representation of muscle pain and mechanical hyperesthesia in the orofacial region: a positron emission tomography study
Pain
(2004) Pro-nociceptive action of cholecystokinin in the periaqueductal grey: a role in neuropathic and anxiety-induced hyperalgesic states
Neurosci. Biobehav. Rev.
(2008)- et al.
Epidemiology of chronic musculoskeletal pain
Best Pract. Res. Clin. Rheumatol.
(2007)
A review of systems and networks of the limbic forebrain/limbic midbrain
Prog. Neurobiol.
Valid conjunction inference with the minimum statistic
Neuroimage
Event-related functional MRI study on central representation of acute muscle pain induced by electrical stimulation
Neuroimage
Central representation of the RIII flexion reflex associated with overt motor reaction: an fMRI study
Neurophysiol. Clin.
Functional imaging of brain responses to pain. A review and meta-analysis (2000)
Neurophysiol. Clin.
Dorsal horn neurons having input from low back structures in rats
Pain
Regional cerebral blood flow during gastric balloon distention in functional dyspepsia
Gastroenterology
Representation of attitudinal knowledge: role of prefrontal cortex, amygdala and parahippocampal gyrus
Neuropsychologia
Region of interest analysis using an SPM toolbox
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