Antinociception produced by an ascending spino-supraspinal pathway

Area of Science:

• Neuroscience
• Pain Research
• Pharmacology

Background:

• Opioid-induced antinociception via intrathecal (i.t.) administration can be inhibited by intracerebroventricular (i.c.v.) naloxone.
• This inhibition suggests supraspinal involvement in opioid-mediated pain relief.

Purpose of the Study:

• To test the hypothesis that i.c.v. naloxone inhibits supraspinal endogenous opioid-mediated antinociception.
• To identify the supraspinal sites where i.t. opioids evoke antinociception.

Main Methods:

• Rats were administered i.t. DAMGO, i.t. lidocaine, or underwent spinal transection.
• The trigeminal jaw opening reflex (JOR) was measured as an indicator of antinociception.
• i.c.v. naloxone or microinjections of naloxone methiodide into specific brain regions (nucleus accumbens, RVM, PAG) were used to assess antagonism.

Main Results:

• i.t. DAMGO, i.t. lidocaine, and spinal transection all produced antinociception, evidenced by JOR attenuation.
• i.c.v. naloxone antagonized these antinociceptive effects.
• Microinjection of naloxone methiodide into the nucleus accumbens, but not RVM or PAG, antagonized the antinociceptive effects of i.t. DAMGO or lidocaine.

Conclusions:

• Findings support an ascending antinociceptive pathway from the spinal cord to supraspinal sites.
• This pathway tonically inhibits supraspinal opioid-mediated antinociception.
• The nucleus accumbens is implicated as a key supraspinal site involved in this opioid-dependent antinociception.