It is evident that there is some neural linkage between the spinal cord dorsal horn and the knee joint that is important in the development of the inflammation. The linkage between the spinal cord dorsal horn and the knee joint that contributes to the development of the inflammation does not seem to be the sympathetic nervous system because a surgical sympathectomy does not affect the development of the inflammation. Spinal administration of bicuculline or dorsal rhizotomies also prevented half of the swelling of the knee joint and the temperature increase. Interrupting the output of preganglionic sympathetic neurons also does not have these effects. In animals that have an intact sympathetic outflow, antagonists of α1 adrenoreceptors or of neuropeptide Y2 receptors reduce the flare and the dorsal root reflexes evoked by a capsaicin injection, but antagonists of α2 adrenoreceptors or of neuropeptide Y1 receptors do not. Evidently, release of norepinephrine acting at α1 adrenoreceptors and of neuropeptide Y acting at neuropeptide Y2 receptors helps maintain the responsiveness of nociceptive afferents to capsaicin and their ability to trigger dorsal root reflexes and flare. The mechanism for this is unclear, although it seems possible that the effects of these neurotransmitters could be mediated indirectly by actions on transient receptor potential vanilloid-1 (TRPV1).

Although the neural links between the knee joint and the spinal cord include sensory afferent fibers and effects of neuropeptides on vasomotor tone, sympathetic output is not responsible for the neurogenic inflammation observed for the knee joint as it is in the skin. The composition of the knee joint nerve is almost entirely small unmyelinated and lightly myelinated sensory nerves. Somatic motor activity also is not involved because inflammation could be produced even when the musculature was paralyzed. The neurogenic link for joint tissues has to be the sensory axons.

The sympathetic nervous system plays a role in the inflammatory process. Specifically, it is thought that the sympathetic nervous system is more involved in chronic inflammation than acute inflammation. Acutely, adrenergic blockers have no effect on inflammation associated with antidromic stimulation of primary afferent fibers. Surgical and chemical sympathectomy or systemic depletion of catecholamines similarly has no effect on the acute inflammation induced by carrageenan. Sympathectomy reduces the severity of injury induced in chronic adjuvant arthritis. These studies suggest that involvement of the sympathetic nervous system is a key difference between acute and chronic inflammation.