EVIDENCE FOR A CENTRAL COMPONENT IN THE SENSITIZATION OF SPINAL NEURONS WITH JOINT INPUT DURING DEVELOPMENT OF ACUTE ARTHRITIS IN CATS KNEE

1. In the spinalized cat, nociceptive spinal neurons with knee input show enhanced responses to mechanical stimulation of that joint once an inflammation has developed in the knee. Enhanced responses may result from increased afferent inflow as well as from modifications of the nociceptive processing within the spinal cord. To examine the significance of these components, we tested in 30 chloralose-anesthetized, spinalized cats whether, during development of arthritis, changes of responsiveness in spinal neurons are restricted to stimulation of the inflamed joint or whether responsiveness in these neurons is altered in general. While continuously recording from a neuron, we injected kaolin and carrageenan into the knee and tested the responses to mechanical stimuli applied to the joint and to regions adjacent to and remote from the knee during the developing arthritis. In addition, in six cats we monitored the neurons' responses to electrical stimulation of the sural nerves and the rostral lumbar spinal cord. 2. Of 32 neurons in laminae VI, VII, and VIII of the lumbar spinal cord, 15 ascending and eight nonascending cells were driven by mechanical stimulation of one or both knee joint(s). Nine of these were nociceptive specific (NS), responding exclusively or predominantly to noxious compression of the knee and other deep tissue, and 12 were wide-dynamic-range (WDR) cells with graded responses to gentle and noxious stimuli applied to the knee joint(s), deep tissue, and skin. Two neurons with high ongoing discharges had some excitatory joint input but showed marked inhibition by most stimuli used (INH neurons). The majority of the neurons had receptive fields on both legs. Nine of the 32 neurons had no input from the knee(s). 3. All 23 neurons with joint input became sensitive or more responsive to movements and gentle compression of the inflamed knee once the inflammation had developed. In general, these neurons also showed enhanced responses to compression of the adjacent muscles in thigh and lower leg. In 20 neurons, response properties were even altered for stimuli applied to regions remote from the inflamed joint, including the contralateral leg in 18 cases. We found expansion of initially restricted receptive fields (mainly in NS cells), enhancement of preexisting responses, and/or lowering of threshold to mechanical stimuli applied to these regions; few neurons developed inhibitory reactions. In all parts of the legs, increased responsiveness was mainly observed for stimuli activating receptors in the deep tissue. Responses to brushing of the skin showed minor changes. 4. The neurons' responsiveness for mechanical stimulation of knee, and adjacent and remote regions, changed in a similar time course, showing the main effects within the 2nd-3rd h after injection of the inflammatory compounds. 5. In addition the excitability of neurons with articular input was tested in four experiments by electrical stimulation of the sural nerves and the spinal cord (sufficient to evoke orthodromically evoked spikes). Once arthritis developed, responses to electrical stimulation increased with a similar time course as the responses to mechanical stimuli. 6. With the same protocol, we studied the nine neurons without joint input. Four ascending cells could initially be driven from the leg but not from the knees. Five neurons were initially only excited by electrical stimulation from the upper lumbar cord but showed no ongoing and no evoked discharges (silent neurons). During the development of arthritis, the four active units without joint input did not change responsiveness to mechanical stimuli nor the size of their receptive fields. Correspondingly, the responses to electrical stimulation did not change in the two neurons tested. Of the five silent neurons, three remained unresponsive but two became excitable by stimulation of the legs. 7. We conclude that in the spinalized cat the arthritis-evoked 'sensitization' of most spinal neurons in laminae VI, VII, and VIII with input from the (inflamed) knee is associated with phenomena that indicate a contribution of spinal mechanisms to this sensitization. The relevance of these results for joint pain is discussed.