Immune and inflammatory mechanisms in neuropathic pain.

Tissue damage, inflammation or injury of the nervous system may result in chronic neuropathic pain characterised by increased sensitivity to painful stimuli (hyperalgesia), the perception of innocuous stimuli as painful (allodynia) and spontaneous pain. Neuropathic pain has been described in about 1% of the US population, is often severely debilitating and largely resistant to treatment. Animal models of peripheral neuropathic pain are now available in which the mechanisms underlying hyperalgesia and allodynia due to nerve injury or nerve inflammation can be analysed.

Chemical mediators enhance the excitability of unmyelinated sensory axons in normal and injured peripheral nerve of the rat.

Ectopic excitation of nociceptive axons by chemical mediators may contribute to symptoms in neuropathic pain. In this study, we have measured the excitability of unmyelinated rat C-fiber axons in isolated segments of sural nerves under different experimental conditions. (1) We demonstrate in normal rats that several mediators including ATP, serotonin (5-HT), 1-(3-chlorophenyl)biguanide (5-HT3 receptor agonist), norepinephrine, acetylcholine and capsaicin alter electrophysiological parameters of C-fibers which indicate an increase of axonal excitability.

T lymphocytes play a role in neuropathic pain following peripheral nerve injury in rats.

A catastrophic consequence of peripheral nerve injury is the development of abnormal, chronic neuropathic pain. The inflammatory response at the injury site is believed to contribute to the generation and maintenance of such persistent pain. However, the physiological significance and potential contribution of T cells to neuropathic pain remains unclear.

Beneficial immune activity after CNS injury: prospects for vaccination.

A recent study in our laboratory showed, against all expectations, that macrophages and a particular type of T cell, by promoting regrowth and reducing the post-traumatic spread of damage in the injured rat optic nerve or spinal cord, have a beneficial effect on the injured CNS. Macrophages in the CNS have long been thought to have predominantly destructive effects. Autoimmunity in general, and in the CNS in particular, has never been documented as a purposeful physiological response of benign character.

Production of neurotrophins by activated T cells: implications for neuroprotective autoimmunity.

Neurotrophins (NTs) promote neuronal survival and maintenance during development and after injury. However, their role in the communication between the nervous system and the immune system is not yet clear. We observed recently that passively transferred activated T cells of various antigen specificities home to the injured central nervous system (CNS), yet only autoimmune T cells specific to a CNS antigen, myelin basic protein (MBP), protect neurons from secondary degeneration after crush injury of the rat optic nerve.