The Role of the Limbic System
After stimulating WDR neurons, afferent input from active MTrPs then ascends the spinothalamic tract to reach higher brain centers, activating the limbic system. The limbic system plays a critical role in modulating muscle pain and the emotional or affective component of persistent pain.3 Increased activity in the limbic system leads to greater fear, anxiety, and stress. For example, Niddam et al. demonstrated increased anterior insula activity in patients with upper trapezius myofascial pain syndrome.13 Insular activity is associated with fear, anxiety, and depression along with fibromyalgia, somatization, and subjective feelings of pain (Figure 11.2).25
The limbic system is part of the brainstem’s descending pain modulatory network leading to myofascial pain. Recent neuroimaging studies have suggested the brain regions associated with several cognitive factors altering pain perception. For example, attention appears to modulate the pain experience through the activity of the amygdala26 and may explain the prevalence of hypervigilance in many chronic pain patients. The anticipation of pain worsens the pain experience and may become maladaptive in chronic pain patients, contributing to avoidance behavior and anxiety.25 In fact, anticipatory anxiety appears to influence pain perception through increased activity in the entorhinal cortex, which subsequently increases activity in other affective pain-processing regions in the brain.26 Even in healthy individuals, anticipation of pain is positively correlated with pain intensity.25 Catastrophizing can intensify pain through rumination, helplessness, and magnification.25
The interrelationship between depression and pain is observed. Experimentally induced pain studies have shown a correlation between the negative mood and an increase in pain perception.
FIGURE 11.2 Centralized factors that influence the pain experience. (Adapted from Tracey I., and Mantyh P.W. The cerebral signature for pain perception and its modulation. Neuron. 2007; 55: 377-391.)
Individuals with chronic musculoskeletal pain conditions and concomitant depression have activation of brain regions related to emotions including the amygdala, anterior insula, and medial prefrontal cortex upon painful stimulation. Behavioral and animal studies suggest that heightened hyperalgesia in those with chronic pain and comorbid depression may be influenced by a lack of descending pain inhibition.25
In addition to influencing the limbic system, negative affect and hormonal fluctuations may then modulate the periaqueductal gray (PAG) in the midbrain and influence the rostral ventral medulla (RVM), contributing to maladaptive neuroplastic changes and neurogenic inflammation (Figure 11.3). The RVM, a relay area between the PAG and the spinal dorsal horn, contains a population of ON cells, which can increase pain perception, and OFF cells, which can decrease pain perception. These ON/OFF cells are part of the descending inhibitory pain system. Following initial tissue injury, the ON cells serve a useful and protective purpose to prevent further damage. Under ordinary circumstances, tissue healing would lead to a decrease in ON cell activity and an increase in OFF cell activity.13 However, in chronic musculoskeletal pain conditions, there appears to be a shift to a decrease in inhibition, presumably due to an imbalance of ON cell and OFF cell activity.27 Thus, over time, maladaptive neuroplastic changes may result in disinhibition in the spinal dorsal horn. As a result, dorsal root reflexes can create a neurogenic inflammation, which then leads to local tissue tenderness, even in the absence of ongoing tissue injury or nociception.
Given the interrelationship among sensitization, the limbic system, and chronic pain in conditions like MPS, clinicians are broadening their focus from not only obtaining pain relief and increasing function, but also to improving the patient’s quality of life. For example, in a study of adults with MPS and active MTrPs compared to those without pain, Gerber et al. assessed quality of life and function, disability, sleep, mood, and range of motion in addition to pain.28 Those with MPS significantly differed from those without MPS not only in their physical findings and self-reported pain levels but also quality of life factors like sleep disturbance, disability, health status, and mood.28 Specifically, significant disability using the Oswestry Disability Scale was associated with
FIGURE 11.3 Role of periaqueductal gray (PAG) and rostral ventromedial medulla (RVM) in the descending modulatory system in response to noxious stimulus. (Adapted from: Tracey I., and Mantyh P.W. The cerebral signature for pain perception and its modulation. Neuron. 2007; 55: 377-391.) active MTrPs, supporting a relationship between MPS and global activity.28 Similarly, Kaergaard and Andersen’s research on female sewing machine operators suggested an increased likelihood of shoulder/neck pain with increased length of employment and decreased social support.29 Such studies emphasize the importance and relevance of assessing daily routines, mood, and health status in addition to physical symptoms to improve pain management.
