Differential impact of psychological and psychophysical stress on low back pain in mice

Abstract

Low back pain (LBP) is a highly prevalent and disabling condition whose initiating factors are poorly understood. It is known that psychological and physical stress is associated with LBP but the causal relationship, mechanisms, and mediators have not been elucidated, and a preclinical model enabling the investigation of causality and thereby critically contributing to clinical translation does not exist. In this study, we first established and characterized a myofascial LBP model in mice based on nerve growth factor (NGF) injection into the low back muscles. Second, we investigated the effect of 2 different stress paradigms on this mouse LBP model by applying the chronic unpredictable stress and vertical chronic restraint stress (vCRS) paradigms, to mimic psychological and psychophysical stress, respectively. In these studies, we combined longitudinal behavioral tests with gene and protein expression analysis in the muscle, dorsal root ganglia, and spinal cord. Nerve growth factor-induced LBP was characterized by long-lasting local and plantar mechanical hypersensitivity, cold hyperalgesia, decreased grip strength and wheel running activity, and time-dependent changes of neuropeptide and glial markers in the spinal cord. Interestingly, the exposure to chronic unpredictable stress slightly worsened pain behavior, whereas vCRS primed and highly aggravated pain in this LBP model, by causing per se the intramuscular upregulation of endogenous NGF and increased spinal astrocyte expression. Our mouse model, particularly the combination of NGF injection and vCRS, suggests that similar mechanisms are important in nonspecific LBP and might help to investigate certain aspects of stress-induced exacerbation of pain.

Evidence of a new hidden neural network into deep fasciae

“…Indeed, it is well recognized that chronic stress can alter the physiological cross-talk between brain and biological systems, leading to compromised functions on the nervous, immune, endocrine, and metabolic systems 16 . This result can help to explain the increased levels of low back pain in patients with chronic stressfull state, a known effect but the mechanisms of which are not yet fully understood 17 .…”

Frequency of Psychosomatic-Prone Myofascial Pain Syndrome in Patients with Incurable Cancer and its Association with the Armchair Sign: A Secondary Analysis of A Prospective, Multicenter, Observational Clinical Study

“…One of the reference criteria of the MPS diagnostic criteria is that pain worsens with stress (7). The relationship between low back pain, such as myofascial pain, and psychological stress has been reported in a study that identi ed aspects of psychological stress-induced pain exacerbation (8). Furthermore, an observational study investigated psychosomatic-prone MPS in cancer patients, which showed that 57.1% of cancer patients with MPS experienced psychological stress (6).…”

Effect of ischemic compression performed by family caregivers on myofascial pain syndrome and the care burden of the families of patients: a multicenter open-label randomized comparative study

“…Patients receiving home care (especially patients with cancer) often have the same posture due to decreased activity, and the prevalence rate of MPS is expected to be high. In addition, the decreased activity is expected to be related to psychological stress (7). Psychological stress has been reported to be associated with low back pain in mice.…”