J Korean Med Sci.  2012 Apr;27(4):430-436. 10.3346/jkms.2012.27.4.430.

Interaction of Morphine and Selective Serotonin Receptor Inhibitors in Rats Experiencing Inflammatory Pain

• Lee BS
• Jun IG
• Kim SH
• Park JY

• KMID: 2157905
• DOI: http://doi.org/10.3346/jkms.2012.27.4.430

Abstract

Citalopram and paroxetine are selective serotonin reuptake inhibitors and also have antinociceptive effects. We investigated the antiallodynic and antihyperalgesic effects of intrathecally administered morphine, citalopram, paroxetine, and combinations thereof, in a rat model in which peripheral inflammation was induced by complete Freund's adjuvant (CFA). Drugs were intrathecally administered via direct lumbar puncture. Mechanical allodynia was measured using a Dynamic Plantar Aesthesiometer. Thermal hyperalgesia and cold allodynia were determined by measuring latency of paw withdrawal in response to radiant heat and cold water. Behavioral tests were run before and 15, 30, 45, and 60 min after intrathecal injection. Intraplantar injection of CFA produced mechanical allodynia, thermal hyperalgesia, and cold allodynia. Intrathecally administered morphine (0.3 or 1 microg) had antiallodynic or antihyperalgesic effects (24.0%-71.9% elevation). The effects of morphine were significantly increased when a combination of citalopram (100 microg) and paroxetine (100 microg) was added (35.2%-95.1% elevation). This rise was reversed by naloxone and methysergide. The effects of citalopram and paroxetine were also reversed by naloxone and methysergide. We suggest that the mu opioid receptor and serotonin receptors play major roles in production of the antiallodynic and antihyperalgesic effects of morphine, citalopram, paroxetine, and combinations thereof, in animals experiencing inflammatory pain.

Keyword

Citalopram; Inflammation; Intrathecal injections; Morphine; Pain; Paroxetine

MeSH Terms

Analgesics, Opioid/administration & dosage/*pharmacology
Animals
Behavior, Animal/drug effects
Citalopram/administration & dosage/pharmacology
Disease Models, Animal
Hyperalgesia/etiology
Inflammation/*chemically induced/pathology
Injections, Spinal
Male
Morphine/administration & dosage/*pharmacology
Pain/*prevention & control
Pain Measurement
Pain Threshold/drug effects
Paroxetine/administration & dosage/pharmacology
Rats
Rats, Sprague-Dawley
Receptors, Serotonin/*chemistry/metabolism
Serotonin Uptake Inhibitors/administration & dosage/*pharmacology
Temperature
Time Factors

Figure

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  Fig. 1 Experimental design: four sets of experiments were conducted. i.t., intrathecal injection.

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  Fig. 2 Time course of mechanical allodynia, thermal hyperalgesia, and cold allodynia after Complete Freund's Adjuvant (CFA) injection. *P < 0.05 vs naïve rats.

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