Curing nerve injury pain in mice

Another boost for mankind from the humble laboratory mouse.

nNOS is neuronal nitric oxide sythase which forms NO in neurons.
iNOS is inducible nitric oxide synthase, which favors neurogenesis and links with CREB

These two synthases turn out to be opposite to each other, although both can increase nitric oxide (NO). Consequently, we cannot simply say NO is a pain neurotrsnsmitter. It depends. There is some reason to suspect that what matters is the aggregate amount of both synthases, since blocking neuronal NOS also blocks nerve injury pain. Clearly, there is more we must learn, although it appears that we may proceed with pain relief by blocking nNOS, while keeping up the search for more understanding of iNOS.

Luo et al in J Neurochem. 2007 Sep 13 more or less shocked researchers by discovering that ischemia (blood deprivation, such as in stroke), which induces neurogenesis in the hippocampus, causes REDUCTION in neuronal nitric oxide synthase, but INCREASES both inducible NOS (iNOS) and CREB phosphorylation (ie. activation of CREB, short for cAMP response element-binding protein). CREB is a pain chemical and is described extensively elsewhere at this site.

Luo’s study suggests that in the attempt to form new neurons in the hippocampus, a stress response, the body may inadvertently CAUSE pain. It would appear that inducible NOS (iNOS) has some role in fostering the growth of new neurons. This makes nNOS and iNOS at odds in their function. Neuronal NOS lowers as inducible NOS elevates! This is surely surprising.

Neuronal nitric oxide synthase (nNOS) is an enzyme responsible for production in neurons of nitric oxide, a neurotransmitter. Rather than repeat what we have written elsewhere about nNOS, we invite you to use SEARCH to review that material.

Blocking nNOS may be a new avenue for pain from nerve injury hypersensitization such as seen in the dorsal horn (rear entry portal) of the spinal cord.

Guan et al in Moecular Pain. 2007 Oct 8;3(1):29 have recently shown that 7 nitroindazole, a potent blocker of nNOS, given intrathecally (spinal fluid) attenuates nerve injury pain in mice. The result was the same in genetically engineered nNOS knockout mice. The evidence looks pretty straightforward. We hope this is a new avenue for help in cases of central pain.