Figure 1

Key elements of osteoarthritis (OA) pain pathophysiology and examples of pharmacological intervention points. Observations of pain resolution following intra-articular local anesthetic and following joint replacement would implicate a peripheral drive in the majority of OA patients. In the periphery, the interaction between structural pathology, and the immune and nervous systems perpetuate the pain experience. Over time, as structural pathology develops, the principle algogenic mechanisms and mediators will change. Furthermore, dysfunction in central processing of information at the spinal and cortical levels has also been observed in OA patients, affecting both sensory and motor systems. This, in combination with altered affective and cognitive functions, may underpin the pain experience in other patient subsets. ASIC, acid-sensing ion channel; BDNF, brain-derived neurotrophic factor; CB, cannabinoid receptor; CCR, chemokine receptor; CGRP, calcitonin gene-related peptide; COX, cyclo-oxygenase; DOR, delta opioid receptor; EP, E prostanoid receptor; FAAH, fatty acid amide hydrolysis; GABA, gamma-amino butyric acid; IL, interleukin; mGluR, metabotropic glutamate receptor; mPGES, membrane or microsomal PGE synthase; N-type Ca²⁺, neuronal-type calcium channels; NE, noradrenaline; NGF, nerve growth factor; NR2B, -N-methyl-D-aspartate receptor 2B subunit; P2X, purinergic 2X ionotropic receptor; SSRI, selective serotonin reuptake inhibitor; SubP, substance P; T-type Ca²⁺, transient type Ca²⁺ channels; TNF, tumor necrosis factor; TNFR, tumor necrosis factor receptor; Trk, tyrosine kinase; TRP, transient receptor potential; VEGF, vascular epidermal growth factor.