Chronic musculoskeletal pain is highly prevalent and presents a major burden to individuals and society. Myofascial pain syndrome can be either acute or chronic and is highly associated with myofascial trigger points in the affected muscles. Spinal segmental sensitization is a hyperactive state of the dorsal horn caused by bombardment of nociceptive impulses from sensitized or damaged tissue including somatic structures or visceral structures. 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. 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. Thus, in addition to the development of standardized diagnostic criteria, studies of sufficient size and power with quantitative outcome measures are sorely needed in order to improve the treatment of chronic musculoskeletal pain and myofascial trigger points.