Involvement of Parvalbumin-Positive Neurons in the Development of Hyperalgesia in a Mouse Model of Fibromyalgia

Abstract

Fibromyalgia (FM) presents as chronic systemic pain, which might be ascribed to central sensitization, in which pain information processing is amplified in the central nervous system. Since patients with FM display elevated gamma oscillations in the pain matrix and parvalbumin (PV)-positive neurons play a critical role in induction of gamma oscillations, we hypothesized that changes in PV-positive neurons are involved in hyperalgesia in fibromyalgia. In the present study, to investigate a role of PV-positive neurons in neuropathic pain, mice received reserpine administration for 3 consecutive days as an animal model of FM (RES group), while control mice received vehicle injections in the same way (VEH group). The mice were subjected to hot-plate and forced swim tests, and immuno-stained PV-positive neurons were counted in the pain matrix. We investigated relationships between PV-positive neuron density in the pain matrix and pain avoidance behaviors. The results indicated that the mice in the RES group showed transient bodyweight loss and longer immobility time in the forced swim test than the mice in the VEH group. In the hot-plate test, the RES group showed shorter response latencies and a larger number of jumps in response to nociceptive thermal stimulus than the VEH group. Histological examination indicated an increase in the density of PV-positive neurons in the primary somatosensory cortex (S1) in the RES group. Furthermore, response latencies to the hot-plate were significantly and negatively correlated with the density of PV-positive neurons in the S1. These results suggest a critical role for PV-positive neurons in the S1 to develop hyperalgesia in FM.

Oxidative Stress in Fibromyalgia: From Pathology to Treatment

“…Selenium is the essential trace element of antioxidative properties, influencing neurotransmission. Unfortunately, selenium level is reduced in FM patients [ 66 , 67 ]. Selenium is a cofactor of the glutathione peroxidase (GSH-Px) enzyme [ 68 ].…”

“…Selenoproteins are necessary for the development of parvalbumin- (PV-) interneurons, a class of GABAergic neurons involved in synchronizing neural activity [ 66 ]. The dysfunctional activity of PV-interneuron networks is involved in hyperalgesia in fibromyalgia, in which pain information processing is amplified in the central nervous system [ 67 ]. Thus, selenium supplementation in deficient FM patients can improve clinical symptoms and benefit the quality of life.…”

The Fibromyalgia Pain Experience: A Scoping Review of the Preclinical Evidence for Replication and Treatment of the Affective and Cognitive Pain Dimensions

“…All identified studies in this review utilizing FST produced indications of depression-like behavior in animals as a result of the model . However, several studies utilized FST as a sole measure of affect [38][39][40][41][42][43][44][45][46][47][48]. While FST is understood to evaluate behavioral despair, which may be related to concepts of learned helplessness [71], these should not be considered unconditionally when employed as a lone measure of affective function.…”