The Neural Cell Adhesion Molecule Antibody Blocks Cold Water Swim Stress-Induced Analgesia and Cell Adhesion Between Lymphocytes and Cultured Dorsal Root Ganglion Neurons

Abstract

This study provides insight into the role of cell adhesion molecules in lymphocyte adhesion to sensory neurons and a link to immune-derived antinociception.

Modulation of Peripheral Sensory Neurons by the Immune System: Implications for Pain Therapy

“…Blocking selectins, ICAM-1, integrins ␣ 4 and ␤ 2 , or chemokines CXCL1 and CXCL2/3 in vivo substantially decreased opioid-producing immune cells in inflamed tissue or injured nerves (Machelska et al, 1998(Machelska et al, , 2004Brack et al, 2004c;Labuz et al, 2009). In addition, the recruitment of opioid-containing cells is dependent on neurokinin-1 receptors (which bind substance P) (Rittner et al, 2007b), on sensory and sympathetic neurons (Kager et al, 2010), and may be regulated by adhesion to neurons (Hua et al, 2006). Central mechanisms also play a role because intrathecally administered analgesic doses of morphine led to a decreased number of END-positive leukocytes in inflamed rat paws (Schmitt et al, 2003).…”

“…Consistent block of selectins, ICAM-1, integrins, CXCL1, or CXCL2/3 in vivo substantially decreases the number of opioid-containing cells in inflamed tissue and abolishes endogenous peripheral opioid analgesia (Machelska et al, 1998(Machelska et al, , 2004Brack et al, 2004c). Stress-induced analgesia is also decreased by blockade of neural cell adhesion molecule, presumably by preventing the adhesion of opioid peptide-producing cells to peripheral nerves in inflamed tissue (Hua et al, 2006). Thus, adhesion molecules have an impact on pain by modulating the extravasation of opioid producing immune cells and/or their adhesion to sensory neurons.…”

Dual Peripheral Actions of Immune Cells in Neuropathic Pain

“…Furthermore, pretreatment of rats with a selectin blocker (fucoidin), selective antibodies against ICAM-1, integrins a 4 and b 2 , or CXCL1 and CXCL2/3 substantially reduced the number of opioid-containing immune cells in inflamed tissue (Brack et al 2004b;Labuz et al 2006;Machelska et al 1998Machelska et al , 2002Machelska et al , 2004. In addition, this cell recruitment is dependent on substance P and neurokinin-1 receptors (Rittner et al 2007) and might be regulated by adhesion to neurons (Hua et al 2006). …”

Endogenous Regulation of Inflammatory Pain by T-cell-derived Opioids

“…6 In a protease-enriched environment, the migration of opioid-producing leukocytes at the vicinity of the sensory nerve endings reduces opioid degradation. 58,59 Thus, the analgesic activity of CD4 + T cells is also dependent on their topographic distribution. Neurons and lymphocytes directly interact by means of cell adhesion molecules.…”