Abstract
BackgroundEarly life experience can cause long-term alterations in the nociceptive processes underlying chronic pain, but the consequences of early life arthritic joint inflammation upon the sensory innervation of the joint is not known. Here, we measure pain sensitivity and sensory innervation in a young, juvenile and adult rodent model of arthritic joints and test the consequences of joint inflammation in young animals upon adult arthritic pain and joint innervation.MethodsUnilateral ankle joint injections of complete Freund’s adjuvant (CFA) (6−20 µl) were performed in young, postnatal day (P)8, adolescent (P21) and adult (P40) rats. A separate cohort of animals were injected at P8, and again at P40. Hindpaw mechanical sensitivity was assessed using von Frey monofilaments (vF) for 10 days. Nerve fibres were counted in sections through the ankle joint immunostained for calcitonin gene-related peptide (CGRP) and neurofilament 200 kDa (NF200).ResultsAnkle joint CFA injection increased capsular width at all ages. Significant mechanical pain hypersensitivity and increased number of joint CGRP + ve sensory fibres occurred in adolescent and adult, but not young, rats. Despite the lack of acute reaction, joint inflammation at a young age resulted in significantly increased pain hypersensitivity and CGRP+ fibre counts when the rats were re-inflamed as adults.ConclusionsJoint inflammation increases the sensory nociceptive innervation and induces acute pain hypersensitivity in juvenile and adult, but not in young rats. However, early life joint inflammation ‘primes’ the joint such that adult inflammatory pain behaviour and nociceptive nerve endings in the joint are significantly increased. Early life joint inflammation may be an important factor in the generation and maintenance of chronic arthritic pain.
Highlights
Life experience can cause long-term alterations in the nociceptive processes underlying chronic pain, but the consequences of early life arthritic joint inflammation upon the sensory innervation of the joint is not known
A considerable number of children and adolescents suffer from joint pain associated with juvenile rheumatic disease; persistent pain is the most common and distressing symptom of juvenile idiopathic arthritis (JIA) [1]
Pain behaviour following complete Freund’s adjuvant (CFA) ankle injection was assessed for 10 days using the reflex withdrawal threshold evoked by punctate mechanical stimulation of the hindpaw (Fig. 2)
Summary
Life experience can cause long-term alterations in the nociceptive processes underlying chronic pain, but the consequences of early life arthritic joint inflammation upon the sensory innervation of the joint is not known. Significant mechanical pain hypersensitivity and increased number of joint CGRP + ve sensory fibres occurred in adolescent and adult, but not young, rats. A considerable number of children and adolescents suffer from joint pain associated with juvenile rheumatic disease; persistent pain is the most common and distressing symptom of juvenile idiopathic arthritis (JIA) [1] Both clinical and experimental studies have highlighted the extent of this pain in young patients despite good disease control [1,2,3,4,5]. Sprouting CGRP+ ve nerve fibres are found in the joints of arthritic humans and are closely associated with neovascularization of the joint following injury [18, 19] It is not known whether sensory nerve sprouting occurs in inflamed joints of young rodents
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