Elsevier

Neuroscience

Volume 55, Issue 1, July 1993, Pages 185-195
Neuroscience

Inflammation of the rat paw enhances axonal transport of opioid receptors in the sciatic nerve and increases their density in the inflamed tissue

https://doi.org/10.1016/0306-4522(93)90465-RGet rights and content

Abstract

The effect of inflammation, induced by unilateral intraplantar injection of Freund's adjuvant, on opioid receptors transported in the sciatic nerve and on opioid receptors present in the paw of the rat was studied by means of in vitro receptor autoradiography using [125I]β-endorphin (human) as ligand. In the absence of inflammation, human β-endorphin binding sites accumulated proximally and distally to a ligature placed on the sciatic nerve in a time-dependent manner, indicating bidirectional axonal transport. Some human β-endorphin binding was also visible in non-inflamed paw tissue. Inflammation of the paw tissue massively increased human β-endorphin binding on both sides of the sciatic nerve ligature and in the ipsilateral paw tissue. In inflamed paw tissue, β-endorphin binding accumulated in the cutaneous nerve fibers as well as in the immune cells infiltrating the surrounding tissue. In the sciatic nerve and paw tissue, β-endorphin binding was displaced by (d-Ala2, N-methyl-Phe4,Gly-ol5)enkephalin and (d-Pen2,d-Pen5)enkephalin, selective μ- and δ-opioid receptor agonists, respectively, and by the universal opioid antagonist naloxone, but not by U-50,488H, a k-selective receptor agonist.

Taken together, these data provide neuroanatomical evidence for local inflammation-induced enhanced axonal transport of opioid receptors in rat sciatic nerve and accumulation in paw tissue.

References (39)

Cited by (300)

  • Immune cell-mediated opioid analgesia

    2020, Immunology Letters
    Citation Excerpt :

    The axonal transport of mu-receptors is increased, which results in their enhanced density at the DRG neuron peripheral terminals. This effect is dependent on electrical neuronal activity and nerve growth factor-induced activation of p38 mitogen-activated protein kinase (MAPK) in peripheral inflamed tissue [19,66–69]. The upregulation and enhanced transport of kappa-receptors were mediated by interleukin [IL]-1β [70,71].

  • The contribution of activated peripheral kappa opioid receptors (kORs) in the inflamed knee joint to anti-nociception

    2016, Brain Research
    Citation Excerpt :

    Some findings have shown that peripheral ORs are localized to dorsal root ganglia cells and primary afferent axons (Coggeshall et al., 1997; Ji et al., 1995; Zhang et al., 1998). These ORs could be upregulated or transported into the peripheral terminal in inflamed tissues (Hassan et al., 1993). Based on these findings, it was hypothesized that activation of peripheral kORs by the intra-articular injection of U50488, a selective kOR agonist, into an inflamed knee joint could exert analgesic effects without side effects.

  • Oxytocin and the modulation of pain experience: Implications for chronic pain management

    2015, Neuroscience and Biobehavioral Reviews
    Citation Excerpt :

    The μ-receptor is abundantly distributed in the amygdala and thalamus; the δ-receptor in the cerebral and limbic cortices; and the κ-receptor within the striatum and hypothalamus (Benarroch, 2012). In addition, the 3 subtypes of opioid receptors are expressed within the superficial laminae of the dorsal horn of the spinal cord, as well as the dorsal root ganglion, and the peripheral nociceptive neurons (Benarroch, 2012; Besse et al., 1990; Hassan et al., 1993; Stein et al., 1996). The distribution of opioids within the CNS is very similar to that of the receptors for the peptide hormone oxytocin.

View all citing articles on Scopus
*

Present address: Department of Anatomy and Histology, Faculty of Veterinary Medicine, Assiut University, Assiut, Egypt.

§

Present address: Department of Anesthesiology, Johns Hopkins Hospital, Baltimore, MD 21205, U.S.A.

View full text