Substance P release from knee joint afferent terminals: modulation by opioids

Area of Science:

• Neuroscience
• Pain Research
• Pharmacology

Background:

• Substance P-like immunoreactivity (SP-LI) is a neuropeptide involved in pain transmission.
• Peripheral nerve activation can lead to the release of neuropeptides from sensory neurons.
• The role of opioid receptors in modulating peripheral neuropeptide release is not fully understood.

Purpose of the Study:

• To investigate the release of SP-LI from the knee joint in cats.
• To determine if antidromic nerve stimulation or capsaicin can induce SP-LI release.
• To examine the modulatory effect of opioid receptor agonists and antagonists on SP-LI release.

Main Methods:

• Cats were anesthetized with halothane.
• Perfusate from the intra-articular space of the knee was collected.
• Sciatic nerve was electrically stimulated or capsaicin was administered intra-articularly.
• SP-LI levels in perfusate were measured using radioimmunoassay.
• Opioid receptor ligands (sufentanil, D-Ala2-D-Leu5-enkephalin, D-Pen2-D-Pen5-enkephalin, U50488H) and naloxone were administered.

Main Results:

• Resting perfusate showed no detectable SP-LI.
• Antidromic sciatic nerve stimulation and intra-articular capsaicin significantly increased SP-LI levels in a stimulus-dependent manner.
• The release of SP-LI was inhibited by mu/delta-selective opioid agonists (sufentanil, D-Ala2-D-Leu5-enkephalin, D-Pen5-enkephalin) in a naloxone-reversible way.
• U50488H, a kappa-selective agonist, did not affect SP-LI release.

Conclusions:

• Peripheral SP-LI is released from small primary afferents in the knee joint upon antidromic activation.
• This release is modulated by activation of peripheral mu/delta opioid receptors located on these afferent terminals.
• These findings suggest a potential mechanism for opioid-mediated analgesia at the peripheral level.