A role for pericytes in chronic pain?

Abstract

Purpose of review: The importance of the blood-brain barrier (BBB) and neuroinflammation in neurodegenerative conditions is becoming increasingly apparent, yet very little is known about these neurovascular functions in nonmalignant disease chronic pain. Neural tissue pericytes play critical roles in the formation and maintenance of the BBB. Herein, we review the important roles of neural pericytes and address their potential role in chronic pain.

Recent findings: Pericytes are implicated in the function of neural microvasculature, including BBB permeability, neuroimmune factor secretion and leukocyte transmigration. In addition, the multipotent stem cell nature of pericytes affords pericytes the ability to migrate into neural parenchyma and differentiate into pain-associated cell types. These recent findings indicate that pericytes are key players in pathological BBB disruption and neuroinflammation, and as such pericytes may be key players in chronic pain states.

Summary: Pericytes play key roles in pathological processes associated with chronic pain. We propose that pericytes may be a therapeutic target for painful diseases that have associated neural vascular dysfunction. Given the paucity of new pharmacotherapies for chronic pain conditions, we hope that this review inspires researchers to unearth the potential role(s) of pericytes in chronic pain sowing the seeds for future new chronic pain therapies.

Figure 1

CNS pericyte ICAM-1 expression is induced in a model of inflammatory pain. A representative ICAM-1⁺ pericyte in the dorsal horn of an inflammatory arthritic mouse. We have evidence that spinal cord pericytes are activated in a model of inflammatory arthritis indicating a CNS vascular response to peripheral inflammation. Arrow indicates cell nucleus or perivascular cell. Arrowhead indicate pericytic finger-like projection. Abbrev. ICAM-1 intercellular adhesion molecule-1.

Figure 2

Summary diagram of the roles pericytes play in CNS vascular biology that could contribute to neuronal sensitization and pain when dysregulated. High pericyte coverage induces high tight junction protein expression maintain low vessel permeability. A loss in pericyte coverage associated in pathological diseases results in decreased tight junction protein expression, consequent increased permeability and loss of vessel integrity. Extravasation of serum pro-nociceptive molecules, and pro-nociceptive and pro-inflammatory immune cell transmigration are likely to lead to neuronal sensitization and an increased pain state. Pericytes are able to migrate into neuronal parenchyma and differentiate into a microglia-like phenotype, this mechanism may also contribute to an increased pain state. Abbreviations: A- astrocyte; BM- basement membrane; EC- endothelial cell; L- leukocyte; M- microglia; P- pericyte; RM- reactive microglia.