The effectivity of opioid analgesics is reduced by CCL2 chemokine

Opioid analgesics are the standard of care in the treatment of serious painful states. Treatment of neuropathic pain states, induced by damage to the nervous system, is especially difficult and opioid analgesics often do not have a beneficial effect. It was shown before that neuropathic states are accompanied with neuroinflammatory changes in the spinal cord and the level of different signaling molecules such as chemokine CCL2 is increased. This work shows that chemokine CCL2 is one of the important factors significantly reducing the effectivity of analgesics acting through opioid receptors. It acts probably directly on neurons and also through activation of microglial cells. Analgesic treatment with opioids has also number of serious unwanted side effects. One of them is a paradoxical increase of sensitivity, hyperalgesia/pain after opioids administration. This work shows that this hyperalgesia may be related to TRPV1 receptors activation. These published results suggest that to improve pain treatment with opioid analgesics, modulation of CCL2 and TRPV1 receptors may be needed, especially in cases of neuropathic pain.

The effectivity of opioid analgesics is reduced by CCL2 chemokine - obrazek1

The inhibition of the opioid agonists induced reduction of painful/nociceptive signaling in the spinal cord dorsal horn by the CCL2 chemokine. The control blue line demonstrates the inhibition of the nociceptive synaptic signaling after the DAMGO application and later (in about 13minutes) its potentiation. DAMGO is µ opioid receptors agonist and simulates thus application of opioid analgesics. The analgesic effect of DAMGO application is completely reversed in the presence of CCL2 chemokine (red line). The purple line demonstrates that the effect of CCL2 is dependent on microglia cells activation as it is prevented by microglia inhibitor minocycline.

Chemokine CCL2 preventsopioid‑inducedinhibitionofnociceptivesynaptictransmission in spinalcorddorsalhorn. Mario Heles, Petra Mrozkova, Dominika Sulcova, Pavel Adamek, Diana Spicarova and Jiri Palecek, JournalofNeuroinflammation (2021) 18:279, DOI, IF=8.23

Laboratory of Pain Research, Institute of Physiology, The Czech Academy of Sciences, Videnska 1083, 142 20 Praha 4, Czech Republic