Abstract
Joint pain is a complex phenomenon that involves multiple endogenous mediators and pathophysiological events. In addition to nociceptive and inflammatory pain, some patients report neuropathic-like pain symptoms. Examination of arthritic joints from humans and preclinical animal models have revealed axonal damage which is likely the source of the neuropathic pain. The mediators responsible for joint peripheral neuropathy are obscure, but lysophosphatidic acid (LPA) has emerged as a leading candidate target. In the present study, male and female Wistar rats received an intra-articular injection of LPA into the right knee and allowed to recover for 28 days. Joint pain was measured by von Frey hair algesiometry, while joint pathology was determined by scoring of histological sections. Both male and female rats showed comparable degenerative changes to the LPA-treated knee including chondrocyte death, focal bone erosion, and synovitis. Mechanical withdrawal thresholds decreased by 20-30% indicative of secondary allodynia in the affected limb; however, there was no significant difference in pain sensitivity between the sexes. Treatment of LPA animals with the neuropathic pain drug amitriptyline reduced joint pain for over 2 hours with no sex differences being observed. In summary, intra-articular injection of LPA causes joint degeneration and neuropathic pain thereby mimicking some of the characteristics of neuropathic osteoarthritis.
Highlights
Peripheral nerve damage is a prominent feature of joint diseases such as osteoarthritis (OA) and rheumatoid arthritis (RA)
The mediators and mechanisms responsible for joint neuropathy are still being worked out; lysophosphatidic acid (LPA) has emerged as a leading contender [12]
Twenty-eight days after local injection of LPA into the knee, male and female joints developed a significant deterioration in structural integrity compared to control
Summary
Peripheral nerve damage is a prominent feature of joint diseases such as osteoarthritis (OA) and rheumatoid arthritis (RA). Ahmed et al reported that 54% of RA patients in their cohort reported severe pain, about a third of which was neuropathic in nature [2]. The sequelae of joint neuropathy are multifarious including impairment of neurovascular control mechanisms, altered proprioception, and the emergence of neuropathic pain [3]. In its most severe form, joint sensory denervation leads to Charcot arthropathy the characteristics of which include extreme bone loss, osteophyte formation, and synovitis. This structural damage partly arises due to a lack of neurosensory feedback from the joint culminating in altered gait and abnormal loading patterns during movement. Afferent nerve depletion has been observed in the joints of patients with OA and
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