These articles [Erren and Reiter, 2009: (http://www.sciencedirect.com/science?_ob=PublicationURL&_tockey=%23TOC%236950%239999%23999999999%2399999%23FLA%23&_cdi=6950&_pubType=J&_auth=y&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=771902ac52fbf3a5a627dda1ca25e3e2); Brajac et al., 2009: (http://www.ncbi.nlm.nih.gov/pubmed/19307064)] are great, and they're on different aspects of light in relation to neuroscience and cancer and other aspects. Brajac et al. (2009) discuss neuropeptides in relation to psoriasis and specific skin sites, etc. It can be difficult to know what to say with some of the issues and research related to light and cancer or neurobiology, and I wasn't meaning to suggest that there's nothing there or anything. I just wanted to make sure that someone who came across that discussion was aware of the different mechanisms. It's interesting that the eyes are the most, I think, densely innervated parts of the face but are rarely possible to "shield" from the sun. UVB and UVA normally reach the surfaces of the eyes at all angles, also, because of atmospheric scattering (I forget which kind for UVB and UVA, but I'll learn more about that), and yet sunglasses generally do not cover the sides of the eyes. Thus, the eyes are probably exposed to UVR from the sides, even in people wearing commonly-used sunglasses. In any case, I wonder if some of the Springtime peak in the incidence of suicide (it peaks in the Spring in the Southern hemisphere, too--in October and November, I think, which are the months corresponding to April and early May) has to do with some kind of transient activation of noradrenergic neurons in the locus ceruleus, resulting from an increase in the firing rates of trigeminothalamic tract neurons or of neurons in the caudal trigeminal nucleus that project to or otherwise influence, by polysynaptic pathways, neurons in the locus ceruleus. The anatomy is so complex that it's hard to say much about that, but some of those articles on migraines and on the use of transcutaneous electrical stimulation sort of give a sense of the types of effects that could occur (although I think transcutaneous electrical stimulation uses high-frequency stimulation, much of the time). I guess it's not really possible to say too much about the anatomy, but I sort of wonder if that springtime suicide-rate increase might not have to do with allergies. It must be partly a change in thermoregulation, resulting from increases in skin temperature, etc. That's really strange. It's difficult to dissociate the allergen effect from the other mechanisms, because the allergens can come and go from day to day and week to week or can follow almost clocklike timecourses, as the specific types of pollen stop being produced and stop affecting specific individuals. But maybe there's someting similar that contributes to seasonal affective disorder and interacts with all of the neurobiological effects of visible light. I mean, the absence of UVB in the winter could interact with the effects of visible light and then produce a transient shock to the brain and thermoregulation in the spring. Also, infrared radiation can release CGRP and substance P into the skin, and the sun puts out massive amounts of infrared radiation. They used cold UV lights in some experiments, and I think they have mirrors or something that controls for the infrared wavelengths. They also sometimes monitor skin temperature, to control for the effect of skin temperature on blood flow or even on neurogenic effects.
I remember seeing some articles--at least one--by J.W. Streilein showing that visible light releases CGRP, via a poorly-defined mechanism involving trigeminal ganglion neurons, into the anterior chamber of the eye or into some other part and contributes, directly or indirectly, to anterior chamber-associated immune deviation (ACAID). I wonder if that might have been partly due to small amounts of UVB or UVA in the light source. I think the Streilein et al. (2000) article (in the Annals of the New York Academy of Sciences--I know the article I'm thinking of is in that journal), in this results list, might be one of them (http://scholar.google.com/scholar?q=Streilein+CGRP+anterior+chamber+associated+immune+deviation&hl=en&lr=), but I'm not sure. I know that innervation is required for ACAID, and visible light definitely contributes to ACAID. ACAID is partly driven by the fact that the blood receives, directly, some of the lymphatic drainage from parts of the eye, because of specialized structures. That's associated with tolerogenicity--lymphatic drainage into the blood and, hence, the spleen. The effects of visible light could interact with the effects of UVB and UVA, though, in the anterior chambers of the eyes, because I remember seeing research showing or implying that afferent action potentials could travel from trigeminal small, unmyelinated fibers (C-fibers, but some people call them something else sometimes, too, and I forget what that is), in one site on the facial skin (the eyelid, say) to the trigeminal nucleus and then, by basically a dorsal root reflex or one of the more specific trigeminal reflexes, induce an efferent action potential, in another C-fiber, that travels to part of the eye and releases CGRP. There's a strange effect of UVB, also, that tends to abolish the substance-P-dependent component of neurogenic inflammation but allow CGRP release to still occur, somewhat. There's some kind of tachyphylaxis to substance P release. Either that or the depletion of both substance P and CGRP from C-fiber terminals, such as in response to UVB, is not really accompanied by a repletion, by axonal transport, of new substance P from the cell body. But that could conceivably contribute to some of the springtime peak in the suicide incidence. A class of antidepressants that was developed and never pursued, past a certain point, was the substance P antagonists. It's possible that, in some people, the neurogenic inflammation keeps gaining ground or that the trigeminal system doesn't completely adapt to it. It's so complicated. What I don't understand is how the transition occurs from neurogenic inflammation to this apparent suppressive effect on neurogenic inflammation that can result from UVB/UVA exposure. It's not depletion of stored CGRP or even substance P, I don't think. But there is that article that showed that reduction in CGRP release, over time, in response to an allergic or inflammatory challenge.
Incidentally, another implication of those mechanisms, found by Gillardon and colleagues and by the other UVB researchers, is that a lot of those immunosuppression experiments may not have all that much validity or may be confounded by neurogenic mechanisms. I can't be sure about it, but what could conceivably happen is this: the rodents could be exposed to UVB on the back, and then the release of substance P and glutamate and CGRP at sites rostral to, say, the T5 dorsal root entry zone could cause efferent action potentials to be initiated at the central terminals of cervical DRG neurons that innervate the skin of the ears. For awhile, at least, they were using ear swelling as a marker of allergic inflammation, if one can believe it. So it's conceivable to me that the UVB on one the back could augment inflammation in the ears. Or actually, what I meant to suggest was that the release of CGRP and SP into the ear skin, in response to the efferent activity of the cervical DRG neurons, could deplete the stores of those neuropeptides by the time the x days post-UVB "challenge" on the ear skin rolled around. Then UVB could appear to have produced "50 percent suppression of contact hypersensitivity" but may just have produced a generalized depletion of substance P and CGRP from C-fibers innervating unexposed skin (I think they cover the ears with tin foil during UVB exposure and then use the ears as the elicitation site for the "contact hypersensitivity" experiments). The procedures used for those animal experiments on UVB-induced immunosuppression are just crazy, in my opinion. I did an earlier version of that old paper and just was shocked by the fact that people used different experimental protocols that were impossible to follow and understand. It's horrendous. In any case, this last section of my posting is not really relevant, but it's interesting to me.
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