Beyond Neurons: Evidence That Immune and Glial Cells Contribute to Pathological Pain States

• Published in: Physiological reviews Vol. 82; no. 4; pp. 981 - 1011
• Main Authors: Watkins, Linda R, Maier, Steven F
• Format: Journal Article
• Language: English
• Published: United States Am Physiological Soc 01-10-2002; American Physiological Society
• Subjects: Animals; Chronic Disease; Chronic pain; Ganglia, Spinal - immunology; Ganglia, Spinal - pathology; Humans; Immune system; Immunity, Cellular - physiology; Intractable pain; Neuroglia; Neuroglia - immunology; Neuroglia - physiology; Neurons; Neurons - immunology; Neurons - physiology; Pain - immunology; Pain - pathology; Pain - physiopathology; Peripheral Nervous System Diseases - immunology; Peripheral Nervous System Diseases - pathology; Peripheral Nervous System Diseases - physiopathology; Physiological aspects; Spinal Nerve Roots - immunology; Spinal Nerve Roots - pathology; United States
• ISSN: 0031-9333; 1522-1210
• DOI: 10.1152/physrev.00011.2002

Department of Psychology and the Center for
Neuroscience, University of Colorado at Boulder, Boulder,
Colorado
Watkins, Linda R. and
Steven F. Maier.
Beyond Neurons: Evidence That Immune and Glial
Cells Contribute to Pathological Pain States. Physiol. Rev. 82: 981-1011, 2002. Chronic pain can occur after peripheral
nerve injury, infection, or inflammation. Under such neuropathic pain
conditions, sensory processing in the affected body region becomes
grossly abnormal. Despite decades of research, currently available
drugs largely fail to control such pain. This review explores the
possibility that the reason for this failure lies in the fact that such
drugs were designed to target neurons rather than immune or glial
cells. It describes how immune cells are a natural and inextricable
part of skin, peripheral nerves, dorsal root ganglia, and spinal cord. It then examines how immune and glial activation may participate in the
etiology and symptomatology of diverse pathological pain states in both
humans and laboratory animals. Of the variety of substances released by
activated immune and glial cells, proinflammatory cytokines (tumor
necrosis factor, interleukin-1, interleukin-6) appear to be of special
importance in the creation of peripheral nerve and neuronal
hyperexcitability. Although this review focuses on immune modulation of
pain, the implications are pervasive. Indeed, all nerves and neurons
regardless of modality or function are likely affected by immune and
glial activation in the ways described for pain.