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Topic: Fresh Research - Nociceptin (Read 335 times) |
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floridian
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Good basic biology of CH - - levels of a natural endorphin like molecule called nociceptin are lower in clusterheads when we go into a cluster phase (compared to 'normal' people), but our level of nociceptin returns to normal when we pull out of the cluster phase. Nociceptin is 'colocalized' with CGRP, which means it shares the same nerves and probably inhibits CGRP. Nociceptin inhibits vasodilation.
Previous Fresh Research posts have talked about CGRP and the fact that CGRP inhibitors are being investigated as treatments for CH. Although it may be a few years till we see something on the market, I am optomistic that this line of research will pay off with better meds.
Quote:Cephalalgia. 2004 Apr;24(4):280-3.
Circulating nociceptin levels during the cluster headache period.
Ertsey C, Hantos M, Bozsik G, Tekes K.
The trigeminal innervation of the dura and its vessels has a prominent role in the mechanism of cluster headache. Nociceptin, an opioid neuropeptide, is the endogenous ligand of the OP-4 receptor, with both algesic and analgesic properties depending on the site of action. Nociceptin and its receptor are expressed by trigeminal ganglion cells where they co-localize with calcitonin gene-related peptide, a marker peptide of the trigeminovascular neurones. Nociceptin inhibits neurogenic dural vasodilatation, a phenomenon related to trigeminovascular activation. To explore its possible involvement in cluster headache, we studied circulating levels of nociceptin when attack-free during the cluster period, and also after the termination of the cluster period, using radioimmunoassay. In 14 cluster headache patients nociceptin levels during the cluster period were significantly lower than in age-, and sex-matched controls (4.91 +/- 1.96 vs. 9.58 +/- 2.57 pg/ml, P < 0.01). After the termination of the cluster period nociceptin levels (8.60 +/- 1.47 pg/ml) were not statistically different from controls. Nociceptin levels did not correlate with age, length of disease or episode length. Lower nociceptin levels during the cluster period may result in a defective regulation of trigeminal activity that might not protect sufficiently against the attacks. |
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| « Last Edit: Mar 22nd, 2004, 4:49pm by floridian » |
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Edski_1
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Re: Fresh Research - Nociceptin
« Reply #1 on: Mar 22nd, 2004, 11:18pm » |
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pg/ml is picogram per milliliter, right? that, very small amounts....wow.  Amazing that levels like that of anything can be detected, let alone posibly have any regulatory effects...
What exactly is a picogram? Ten to the minus 12?
If it is a missing chemical then hopefully it can help for better meds. At least it's good to stretch my mind and reacquaint myseslf with some chemistry and analytical chemistry concepts... 
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floridian
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Re: Fresh Research - Nociceptin
« Reply #2 on: Mar 23rd, 2004, 8:36am » |
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I ran a search on 'nociceptin and migraine' and came across this article by Dr. Goadsby.
Quote:Neuropharmacology. 2002 Nov;43(6):991-8.
The ORL-1 (NOP1) receptor ligand nociceptin/orphanin FQ (N/OFQ) inhibits neurogenic dural vasodilatation in the rat.
Bartsch T, Akerman S, Goadsby PJ.
The effects of the ORL-1 (NOP(1)) receptor ligand nociceptin (N/OFQ) and the nociceptin antagonists [Nphe(1)]N/OFQ-(1-13)-NH(2) (Nphe) and nocistatin (NST) on neurogenic dural vasodilatation (NDV) in the rat dura mater evoked by electrical stimulation of a closed cranial window were studied. The middle meningeal artery was visualised using intravital microscopy, and the vessel diameter analysed using a video dimension analyser. N/OFQ (1, 10, 100 nmol kg(-1); i.v., n=10) significantly and dose-dependently suppressed NDV maximally by 65% (P<0.01). Neither Nphe (100 nmol kg(-1); n=5) nor NST (100 nmol kg(-1); n=4) alone had an effect on NDV (P>0.05). Baseline vessel diameter was not significantly affected by application of N/OFQ, NST or Nphe. Application of the selective N/OFQ antagonist Nphe (10, 100 nmol kg(-1) i.v., n= dose-dependently and significantly (P<0.01) reversed the inhibition of NDV induced by application of N/OFQ (10 nmol kg(-1)). NST (10, 100 nmol kg(-1); n=7) failed to reverse the effects elicited by N/OFQ. Application of N/OFQ elicited a dose-dependent transient decrease in arterial blood pressure (P<0.01). Nphe dose-dependently reversed the cardiovascular effects induced by application of N/OFQ (10 nmol kg(-1)) (P<0.01),while NST did not alter the blood pressure reaction elicited by N/OFQ. The results show that N/OFQ inhibits NDV, an effect which is antagonised by Nphe, but not by NST. ORL-1 (NOP(1)) receptors located on trigeminal sensory fibres may be involved in the regulation of dural vessel diameter and hence may play a role in migraine pathophysiology.
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HypnoticFreddy
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Re: Fresh Research - Nociceptin
« Reply #3 on: Mar 23rd, 2004, 9:58am » |
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The pico- prefix is one/trillioneth of a unit. So 10 to the -12 is correct.
-Freddy
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Edski_1
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Re: Fresh Research - Nociceptin
« Reply #4 on: Mar 23rd, 2004, 6:03pm » |
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I remeber the analogy being made in college as to why opiate were so addictive was that the brain made endorphins that were basically natural opiates...and taking opiate drugs overwhelmed the body so that the body didn't sense the "need" to produce any of the natural endorphins...
Hence you were hooked.
Perhaps a similar mechanism explains why opiates might not be efective treating CH, but here's evidence that while we are in cycle a natural opiate is deficient...in extremely low levels. I think that's the key...500 mg of hydrocodone would be roughly a billion times more "opiate" that these regulatory levels need to be...neglecting blood volume...
But considering the huge magnitude of that girst number, a couple of thousand ml of blood isn't going to change the concentrations much.
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