Cyclo-oxygenase-2-immunoreactive neurons in the lumbar dorsal horn in a chicken acute inflammation model

Abstract

Acute and chronic peripheral inflammation is known to induce the expression of cyclo-oxygenase (COX)-2 in spinal cord neurons and increase the synthesis and release of prostaglandins (PG). Although these PG are presumed to cause inflammatory pain or hyperalgesia, the relationship between PG-producing cells in the dorsal horn and substance P (SP)-containing, pain-transmittimg nerve fibers remains unknown. In the present study we investigated immunohistochemically changes in the number of COX-2-containing neurons using the avidin-biotinylated peroxidase complex method in dorsal horn superficial laminae in chicken lumbosacral enlargement (L4, L5) under inflammatory conditions induced by unilateral intraplantar injection of complete Freund's adjuvant. After 12-24 h, a significant increase in the number of small COX-2-containing neurons was observed in lamina II on the injected side compared with the contralateral side. Furthermore, using fluorescent double-labeling for COX-2 and SP, an increase in the number of small COX-2-containing neurons in contact with SP-containing elements was observed ipsilaterally (1.4-1.6-fold compared with the contralateral side) in lamina II. Fluorescence triple-labeling of COX-2, SP and calcitonin gene-related peptide (CGRP) confirmed that the majority of these SP-containing elements coexisted with CGRP, indicating that these elements originated from primary afferent neurons. Using electron microscopy, two types of SP-containing axon terminals were found to form synapses with COX-2-containing neurons in lamina II. These results indicate that the number of COX-2-containing neurons increases concomitantly with an increase in the number of contacts of these neurons with SP-containing primary afferent fibers and suggest that this phenomenon is associated with PG production and the persistence of inflammatory pain.

Fluence-dependent effects of low-level laser therapy in myofascial trigger spots on modulation of biochemicals associated with pain in a rabbit model

“…The relationships among COX-2, TNF-α, and SP have been demonstrated in animals with inflammation-induced hyperalgesia [28,29]. The endogenous opioid peptide, β-ep, seems to be primarily responsible for this intrinsic analgesia.…”

Inflammatory Hyperalgesia: The Role of the Prostaglandin System in the Spinal Cord

“…This hyperalgesia is dependent on COX-2 in the spinal cord [55][56][57], as in the case of hyperalgesia by carrageenan. In contrast, however, several studies showed that cells expressing COX-2 in the spinal cord were neurons but not endothelial cells [58][59][60]. Furthermore, some studies indicated the involvement of IL-1␤ and TNF-␣ in the induction of COX-2 [59,61].…”

Molecular characterization of prostaglandin F receptor (FP) and E receptor subtype 3 (EP3) in chickens

“…On the other hand, the role of prostaglandins in nociception is considerably substantiated in birds, with supporting evidence such as a concomitant increase between the number of contacts between synapses of substance P (SP)-containing, pain-transmitting nerve fibers and the number of cycloxygenase-2 (COX-2; inducible rate-limiting enzyme in prostaglandin-biosynthetic pathway)-containing neurons in dorsal horn [59]. While knockout of EP 3 resulted in impaired febrile response in mice [51] and EP 3 agonists enhanced sensitivity of bradykinin receptors and their consequent inflammatory-related pain response in dogs [18], the role of EP 3 in avian inflammatory pain model is yet unexplored.…”