Increased Calcitonin Gene-Related Peptide Expression in DRG and Nerve Fibers Proliferation Caused by Nonunion Fracture in Rats

Background: Platelet-rich plasma (PRP) has emerged as a treatment for osteoarthritis (OA). However, the effect that leukocyte concentrations in PRP have on OA remains unclear. Purpose: To clarify the optimal PRP formulation for OA treatment by comparing pure PRP, leukocyte-poor PRP (LP-PRP), and leukocyte-rich PRP (LR-PRP) in a rat arthritis model. Study Design: Controlled laboratory study. Methods: Knee arthritis was induced bilaterally in male Wistar rats with intra-articular injections of monosodium iodoacetate (MIA) on day 0. Rats were randomly assigned to 1 of 3 treatment groups (pure PRP, LP-PRP, and LR-PRP). On day 1, allogenic PRP was injected into the right knee of rats and phosphate-buffered saline was injected into the left knee as a control. Weight distribution on the hindlimbs was measured for 14 days to assess pain behavior. Rats were euthanized at day 5 or 14 for histological assessment of synovial tissue and cartilage. Immunohistochemical staining of calcitonin gene-related peptide (CGRP) and α-smooth muscle actin was performed to determine the mechanism of pain relief induced by the PRP preparations. Results: In all groups, PRP increased the load-sharing ratio on PRP-injected knees, with pure PRP eliciting the largest effect among the 3 kinds of PRP ( P < .05). Structural changes in the synovial tissue were significantly inhibited in the pure-PRP group compared with the control group after both 5 and 14 days ( P < .001 and P = .025, respectively), whereas no significant difference was found between the control, LP-PRP, and LR-PRP groups. An inhibitory effect on cartilage degeneration was observed only in the pure-PRP group on day 14. Pure PRP also significantly inhibited expression of CGRP-positive nerve fibers in the infrapatellar fat pad compared with the other groups ( P < .05). Conclusion: In an MIA-induced arthritis model, pure PRP injection was the most effective treatment for reduction of pain-related behavior and inhibition of synovial inflammation and pain sensitization. Clinical Relevance: PRP formulations should be optimized for each specific disease. This study shows the superiority of pure PRP for treatment of arthritis and joint pain.

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Calcitonin gene-related peptide in human nasal mucosa

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1990.258.2.l81 ◽

1990 ◽

Vol 258 (2) ◽

pp. L81-L88 ◽

Cited By ~ 3

Author(s):

J. N. Baraniuk ◽

J. D. Lundgren ◽

J. Goff ◽

J. Mullol ◽

S. Castellino ◽

...

Keyword(s):

Nasal Mucosa ◽

Binding Sites ◽

Calcitonin Gene Related Peptide ◽

Nerve Fibers ◽

Potential Range ◽

Submucosal Gland ◽

Human Nasal Mucosa ◽

Related Peptide ◽

Glandular Secretion ◽

Calcitonin Gene

To explore the potential range of functions for calcitonin gene-related peptide (CGRP) in human mucosa, we quantified human inferior turbinate nasal mucosal CGRP content by radioimmunoassay, localized CGRP-immunoreactivity by immunohistochemistry, detected 125I-CGRP binding sites by autoradiography, and tested the ability of CGRP to induce submucosal gland secretion in short-term explant culture of human nasal mucosa. Nasal mucosa contained 0.45-0.54 pmol CGRP/g wet wt (n = 18). Immunoreactive CGRP was found in nerve fibers that densely innervated the walls of small muscular arteries arterioles. Venules and venous sinusoids were innervated by individual CGRP staining fibers. Occasional CGRP-containing nerve fibers were also noted adjacent to submucosal gland acini, near the epithelial basement membrane, and between epithelial cells. Specific 125I-CGRP binding sites were concentrated on small muscular arteries and arterioles. CGRP (4 microM) did not stimulate glycoconjugate or lactoferrin release from mucosal explants. These results indicate that in the human nasal mucosa, CGRP is present in nerve fibers, which most likely represent nociceptive sensorimotor nerves that innervate vascular structures (muscular arteries, arterioles, veins and venous sinusoids). It is likely that CGRP release from sensory neurons may play a role in the regulation of vasomotor responses, but no evidence for a role of CGRP in glandular secretion was found.

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