Semaphorin 3A or its equivalent, might well prevent Central Pain in the near future if given at the time of cord injury.
Many sensory neurons have their cell bodies in the dorsal root ganglia, just outside the cord and have extensions projecting into the cord.
It has been known for a very long time that deafferented (cut) pain neurons attempt to regrow, forming sprouts, which take on roughly the shape of a cone, known as the “growth cone”. These sprouts are fierce and laden with all the pain producing chemicals one could ever desire. In its mad attempt to regrow the neuron cannot differentiate between growth and production of pain chemicals, which are part of the inflammatory process known as neuroinflammation.
There have been a rash of articles recently on the signalling molecules which appear at the growth cone. Interestingly, a drug known as semaphorin 3 A, which has also seen activity in cancer research for its ability to inhibit growth of blood vessels, also inhibits the growth cone. Inhibit might not be the right word, since it causes COLLAPSE of the growth cone.
See Rabchevsky AG.Prog Brain Res. 2006;152:265-74.
Segmental organization of spinal reflexes mediating autonomic dysreflexia after spinal cord injury.
Wanigasekara Y, Keast JR.Neuroscience. 2006 Oct 13;142(2):369-79.
Nerve growth factor, glial cell line-derived neurotrophic factor and neurturin prevent semaphorin 3A-mediated growth cone collapse in adult sensory neurons.
What is interesting is that nerve growth factor (NGF) and glial cell derived neurotrophin (GDNF) can oppose Sema3A and Sema3A can oppose NGF and GDNF. Neurturin (NTN) is also an opponent of Sema3A and vice versa. These chemicals oppose each other. Not only is somatosensory (body surface) central pain the result of NGF, but the autonomic dysreflexia of SCI is also the product of its action, as it occurs in the visceral/sympathetic relays. (You can review the role of NGF in central pain by using SEARCH at this site).
It is far from proven, but if the growth cones can be destroyed in deafferented cord neurons, it seems that central pain might be preventable. The general rule, as stated by Dr. Patrick Wall (originator of the Wall/McHenry database and painonline itself) is that “Peripheral injury induces Central change.” There are TWO major components of central pain, Spontaneous Pain and Evoked Pain. however, even spontaneous pain may merely be the burnout carried up to brain levels from peripheral hypersensitivity gone wild early in the cord injury. If SemaA can stop growth cones, perhaps it can block evoked pain which is easily the most severe form of dysesthetic burning. It may even halt the development of central changes if given early.
We are happy to see the distinguished scientists at Louisville continue their magnificent work on pain. They have long been knowledgable about protopathic burning, the type of burning manifest in central pain dysesthesia.
More on Sema3A is sure to come. We hope the news is good. Would it ever help those who ALREADY have CP? We just don’t know. Perhaps it could play a role in ending evoked pain, which is perhaps 90% of the really horrible agony suffered in CP, so we are certainly paying attention.