Abstract
The NMDA receptor is central in the generation and maintenance of chronic pain. This receptor has several sites of modulation. One is the glutamate recognition site that can be blocked by (±)-3-(2-carboxypiperazin-yl)propyl-1-phosphoric acid or (±)-CPP. We investigated whether the effect of glial inhibition produced by propentophylline (PPF) can be enhanced when combined with (±)-CPP. We used Sprague-Dawley rats with experimental monoarthritis, administering intrathecally the ED30 for both drugs (3.97 μg of (±)-CPP and 1.42 μg of PPF), since this combination produces an antinociceptive supra-additive effect when used in mechanical nociception (Randall-Selitto test). The combination of (±)-PPF and CPP produced an antinociceptive effect which was greater than that each drug alone as tested by both the C reflex and windup. We conclude that the antinociceptive effect of the combination of (±)-PPF and CPP possibly generates a supra additive interaction type in monoarthritic rats.
Highlights
Pain continues to be a clinical problem difficult to solve for a significant proportion of patients due to the incomplete knowledge we have about the adaptive changes that occur in the neural substrates of the nociceptive system and glial cells in response to episodes of persistent pain
The administration of the ED30 PPF for 10 days did not produce a significant change on the area under the curve (AUC) compared to saline control (Figure 1(a))
The i.t. injection of the ED30 of (±)-CPP resulted in a significant increase in the antinociceptive activity, being 22 times greater than the saline control group in the C reflex (AUC for (±)-CPP was 4265 ± 200)
Summary
Pain continues to be a clinical problem difficult to solve for a significant proportion of patients due to the incomplete knowledge we have about the adaptive changes that occur in the neural substrates of the nociceptive system and glial cells in response to episodes of persistent pain These changes primarily are associated with chronic inflammation processes or injury to peripheral and central nerves. Chronic activation of nociceptors by different chemical mediators induces hypersensitivity or nociceptive sensitization, which is reflected in changes in the basal activation levels of neurons and altered gene transcription (plasticity) This allows the appearance of hyperalgesia or an exaggerated response to a nociceptive stimulus and allodynia, or a nociceptive response against an innocuous stimulus [1]. Great advances in this field occurred in the 1980’s when two groups demonstrated that NMDA receptor antagonists inhibit the hyperexcitability of nociceptive neurons in the spinal cord induced by stimulation of C fibers [2, 3]
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