Localization of SP‐ and CGRP‐immunopositive nerve fibers in the hip joint of patients with painful osteoarthritis and of patients with painless failed total hip arthroplasties

Abstract

Using immunohistochemical methods we determined the presence of SP- and CGRP-immunopositive nerve fibers in the hip joint of patients with femoral neck fracture (controls, group 1), painful osteoarthritis (group 2), and painless failed total hip arthroplasties (group 3). Immunoreactive nerve fibers were found in the soft tissue of the fossa acetabuli as well as in the subintimal part of the synovial layer in the hip joint capsule of groups 1 and 2. In the capsule of controls the innervation density had a median of 5.7fibers/cm(2) for CGRP-ir and 3.2fibers/cm(2) for SP-ir afferents. In the osteoarthritic group, the density significantly increased to a median of 15.6fibers/cm(2) for CGRP-ir and 8.2fibers/cm(2) for SP-ir neurons (p=0.05). Patients with failed hip arthroplasties completely lacked these neuropeptide containing afferents. Innervation density in the fossa acetabuli of osteoarthritc patients showed a median of 14.1fibers/cm(2) for CGRP-ir and 5.9fibers/cm(2) for SP-ir afferents. From these data we assume that the hip joint capsule and the soft tissue of the fossa acetabuli are important triggers of nociception. This is supported by the fact, that patients with loosened total hip arthroplasties, where we failed to detect SP- and CGRP-immunoreactive fibers, did not feel pain. The upregulation of SP- and CGRP-positive neurons in response to arthritic stages suggests a mechanism involving neuropeptides in the maintenance of a painful degenerative joint disease and in mediating noxious stimuli from the periphery. Furthermore, these findings help to explain clinical observations, such as effectiveness of local therapy to control hip pain with intraarticular injection, synovectomy and denervation procedures.

Neuropathic pain in patients with osteoarthritis of hip joint

“…Historically, the mechanism of OA pain has been considered to be of nociceptive origin, but our study identified 5.9% of our hip OA patients as likely to have NP. Regarding the mechanism of NP in hip OA, we have formulated the hypothesis that NP occurs in association with damage to nerves innervating subchondral bone [22], ligamentum capitis femoris [23], capsule [23][24][25]27], the soft tissues of the fossa acetabuli [24], labrum [26] or synovial membrane [27]. Torrance et al [28] reported the results of an epidemiological survey in the UK using S-LANSS [29], the selfcompleted version of the Leeds Assessment of Neuropathic Symptoms and Signs pain scale [30].…”

Synovial macrophage-derived IL-1βregulates the calcitonin receptor in osteoarthritic mice

“…Consistent with this finding, higher expression of IL-1b was observed in synovial macrophages which, when depleted by the treatment of mice with liposomal clodronate, led to decreased IL-1b gene expression in ST. Taken together, these findings indicate that IL-1b is produced mainly by macrophages in synovium. Numerous studies have implicated the involvement of CGRP in the peripheral mechanisms of OA pain [6,[17][18][19][20][21][22]. For example, suppression of the expression of CGRP in the synovium of an adjuvant-induced arthritis rat model has been shown to attenuate the pain [17].…”

High levels of substance P and CGRP in pseudosynovial fluid from patients with aseptic loosening of their hip prosthesis

“…The involvement of neurogenic inflammation in adjuvant-induced experimental arthritis has been demonstrated in rats (Levine et al 1984). SP-and CGRP-immunopositive nerve fibers in the joints of patients with painful osteoarthritis of the hip have been found in the soft tissue of the fossa acetabuli, as well as in the synovial layer of the hip joint capsule (Saxler et al 2007). Joints with severe arthritis have a dense innervation of SP-containing sensory neurons and a higher SP content than joints that develop mild arthritis (Weidler et al 2005).…”