**Summary of process of pain perception**


Tissue injury results in the release of inflammatory mediators such as serotonin, bradykinin, calcitonin gene-related peptide (CGRP) and SP, which lead to nociceptor nerve fibre sensitisation in peripheral tissue. These damaged fibres release inflammatory agents causing a spread of increased sensitivity around the area of tissue damage. This is called primary hyperalgesia. The repeated depolarisation of primary afferent fibres leads to a continuous release of neurotransmitters onto the secondary neurons in the spinal cord, resulting in central sensitisation and secondary hyperalgesia. Peripheral pain sensitisation is a feature of osteoarthritis in the joint.

In addition to peripheral pain sensitisation pain in OA, could also be due to local and central sensitisation of pain, pathways resulting in normal stimuli becoming painful with inflammation being an important feature in the process of OA.

Most of the substances involved in inflammation such as proinflammatory cytokines and bradykinins interact with the nociceptive fibres present within the joint and induce hyperalgesia and allodynia seen in patients with chronic inflammatory joint disease like OA. These mechanisms acting in concert could participate in the progression of hyperalgesia to chronicity.
