Modulation of peripheral endogenous opioid analgesia by central afferent blockade

Modulation of peripheral endogenous opioid analgesia by central afferent blockade

Schmitt TK; Mousa SA; Brack A; Schmidt DK; Rittner HL; Welte M; Schafer M; Stein C

Anesthesiology

2003

Male; Analgesics; Animals; Rats; Injections; Immunohistochemistry; Spinal; Enkephalin; beta-Endorphin/metabolism; Wistar; Pain Threshold/drug effects; Neurons; Afferent/drug effects; Central Nervous System/drug effects; Endorphins/metabolism/physiology; Flow Cytometry; Foot/pathology; Inflammation/pathology; Methionine/metabolism; Morphine/administration & dosage/pharmacology; Opioid/administration & dosage/pharmacology; Peripheral Nerves/drug effects; Psychomotor Performance/drug effects

BACKGROUND: Peripheral tissue injury causes a migration of opioid peptide-containing immune cells to the inflamed site. The subsequent release and action of these peptides on opioid receptors localized on peripheral sensory nerve terminals causes endogenous analgesia. The spinal application of opioid drugs blocks the transmission of nociceptive information from peripheral injury. This study investigates the influence of exogenous spinal opioid analgesia on peripheral endogenous opioid analgesia. METHODS: Six and forty-eight hours after initiation of continuous intrathecal morphine infusion and administration of Freund's complete adjuvant into the hind paw of rats, antinociceptive and antiinflammatory effects were measured by paw pressure threshold, paw volume, and paw temperature, respectively. Inflammation and quantity of opioid-containing cells were evaluated by immunocytochemistry and flow cytometry. Cold water swim stress-induced endogenous analgesia was examined 24 h after discontinuation of intrathecal morphine administration. RESULTS: Intrathecal morphine (10 micro g/h) resulted in a significant and stable increase of paw pressure threshold ( P 0.05). At 48 but not at 6 h after Freund's complete adjuvant, the number of beta-endorphin-containing cells and cold water swim-induced antinociception were significantly reduced in intrathecal morphine-treated rats compared with those treated with intrathecal vehicle ( P< 0.05). CONCLUSIONS: These findings suggest an interplay of central and peripheral mechanisms of pain control. An effective central inhibition of pain apparently signals a reduced need for recruitment of opioid-containing immune cells to injured sites.

2003

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