Spinal glia and proinflammatory cytokines mediate mirror-image neuropathic pain in rats

Autor: Steven F. Maier, Erin D. Milligan, David Martin, Joseph C. Biedenkapp, Marucia Chacur, Linda R. Watkins, Stephen Poole, Carin M. Twining, Kevin O'Connor, Kevin J. Tracey
Předmět:
Male
medicine.medical_specialty
Sialoglycoproteins
p38 mitogen-activated protein kinases
Inflammation
p38 Mitogen-Activated Protein Kinases
Antibodies
Receptors
Tumor Necrosis Factor
Article
Proinflammatory cytokine
Rats
Sprague-Dawley
Internal medicine
medicine
Animals
Citrates
Enzyme Inhibitors
Injections
Spinal
Pain Measurement
Aconitate Hydratase
Neurons
Behavior
Animal
Interleukin-6
business.industry
General Neuroscience
Anti-Inflammatory Agents
Non-Steroidal
Hydrazones
Rats
Disease Models
Animal
Interleukin 1 Receptor Antagonist Protein
Tumor Necrosis Factor Decoy Receptors
Endocrinology
Allodynia
Spinal Cord
Hyperalgesia
Receptors
Tumor Necrosis Factor
Type I
Anesthesia
Neuropathic pain
Cytokines
Neuralgia
Tumor necrosis factor alpha
Body region
Sciatic nerve
Mitogen-Activated Protein Kinases
Sciatic Neuropathy
medicine.symptom
Carrier Proteins
business
Neuroglia
Zdroj: Scopus-Elsevier
Popis: Mirror-image allodynia is a mysterious phenomenon that occurs in association with many clinical pain syndromes. Allodynia refers to pain in response to light touch/pressure stimuli, which normally are perceived as innocuous. Mirror-image allodynia arises from the healthy body region contralateral to the actual site of trauma/inflammation. Virtually nothing is known about the mechanisms underlying such pain. A recently developed animal model of inflammatory neuropathy reliably produces mirror-image allodynia, thus allowing this pain phenomenon to be analyzed. In this sciatic inflammatory neuropathy (SIN) model, decreased response threshold to tactile stimuli (mechanical allodynia) develops in rats after microinjection of immune activators around one healthy sciatic nerve at mid-thigh level. Low level immune activation produces unilateral allodynia ipsilateral to the site of sciatic inflammation; more intense immune activation produces bilateral (ipsilateral + mirror image) allodynia. The present studies demonstrate that both ipsilateral and mirror-image SIN-induced allodynias are (1) reversed by intrathecal (peri-spinal) delivery of fluorocitrate, a glial metabolic inhibitor; (2) prevented and reversed by intrathecal CNI-1493, an inhibitor of p38 mitogen-activated kinases implicated in proinflammatory cytokine production and signaling; and (3) prevented or reversed by intrathecal proinflammatory cytokine antagonists specific for interleukin-1, tumor necrosis factor, or interleukin-6. Reversal of ipsilateral and mirror-image allodynias was rapid and complete even when SIN was maintained constantly for 2 weeks before proinflammatory cytokine antagonist administration. These results provide the first evidence that ipsilateral and mirror-image inflammatory neuropathy pain are created both acutely and chronically through glial and proinflammatory cytokine actions.
Databáze: OpenAIRE
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