The Contribution of Joint Afferent Nerves to the Pathophysiology of Arthritis

Scott, Dugald T (1994) The Contribution of Joint Afferent Nerves to the Pathophysiology of Arthritis. PhD thesis, University of Glasgow.

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The contribution made by joint afferent nerves to the pathogenesis of arthritis can be summarised in relation to particular areas of the afferent pathway. 1. At the peripheral nerve terminals the release of neurotransmitters contributes to the inflammatory process by increasing vascular permeability and reducing vascular resistance. This 'process has been termed neurogenic inflammation. 2. When the action potentials reach the central terminals in the spinal cord, the overall afferent input to muscle efferent nerves is altered. This changes normal reflex patterns which may lead to joint deformity. 3. Relay of the signals to higher centres produces the sensation of pain and an altered awareness of limb position, both of which may lead to altered joint use and joint deformity. The experimental work undertaken in the production of this thesis is concerned with the first two points above. It was found that the neuropeptides substance P (SP) and neurokinin A (NKA) both produce a protein extravasation into the knee joint of the rat. Intra-articular perfusion of the joint with substance P results in protein extravasation into the synovial cavity. The response is dose dependent from 10nM to 10muM. The protein content of the aspirated fluid from the synovial cavity rises for 12-16 minutes before falling sharply over an equivalent period, despite continuous perfusion with SP. The same transient response is observed with NKA. A preceding joint inflammation enhances the effect of substance P, and alters the response from a transient one to a persistent extravasation during SP perfusion. The inhibition of the SP response by the NK-1 receptor antagonist FK888 suggests an involvement of NK-1 receptors in protein extravasation. The inability of FK888 to reduce NKA induced extravasation, together with the inhibition of the NKA response with the NK-1 and NK-2 antagonist FK224, suggests the involvement of NK-2 receptors. In the cat knee joint, the frequency response of low threshold joint afferents in the posterior articular nerve (PAN) to mechanical indentation of the joint capsule was shown to be independent of receptor type. Mechanical stimulation of these receptors reflexly excites a-motoneurones with a latency suggesting a di- or tri-synaptic pathway. This excitation can be reduced by conditioning electrical, or chemical, excitation of high threshold joint afferents. alpha-motoneurones also display a period of excitation, of similar latency to the alpha-motoneorones, in response to electrical stimulation of low threshold joint afferents. Again, a preceding electrical stimulation of high threshold joint afferents inhibits the period of excitation induced in the ?-motoneurone by the low threshold joint afferents. The interaction of the high threshold afferents with the low threshold afferents, without a direct effect on the motoneurones, suggests the possibility of a presynaptic influence on the low threshold joint afferents. It was shown that a conditioning electrical stimulation of the high threshold afferents in the PAN of the cat knee joint increases the intraspinal electrical threshold for antidromic stimulation of group II afferents in the PAN. This suggests a hyperpolarisation of the group II PAN terminals by the high threshold afferents, and this effect may account for the inhibition of the group II induced excitation of the motoneurones. The protein extravasation induced by neuropeptides and the alteration of reflex responses by high threshold afferents may contribute to the pathology of the arthritic joint.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Additional Information: Adviser: Bill Ferrell
Keywords: Neurosciences, Pathology
Date of Award: 1994
Depositing User: Enlighten Team
Unique ID: glathesis:1994-75564
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 19 Nov 2019 19:26
Last Modified: 19 Nov 2019 19:26

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