Neutralizing Peripheral Nociceptors For Pain Relief?

Watson350

Member
Joined
Jun 19, 2017
Messages
153
I have nerve damage in my nose bilaterally on either side of the nasal bones and was curious if anyone has any experience with decreasing localized NO levels either through a topical solution or some sort of RNA hack like Methylne Blue. Ray Peat emailed back with a bunch of articles listed below that involve topics such as localized hyperthermia of the overlying skin caused by regional vasodilation induced by nitric oxide. I just dont have a panacea for myself except to say that Vitamin E seems to help.

J Pain Symptom Manage. 1997 Oct;14(4):225-54.
Role of nitric oxide in the physiopathology of pain.
Anbar M, Gratt BM.
Many painful disorders, including joint dysfunctions such as rheumatoid arthritis (RA) or temporomandibular joint disorders (TMD), are associated with hyperthermia of the overlying skin. The same is true of certain intractable chronic pain conditions, such as chronic orofacial pain, which may be associated with TMD. We suggest that this skin hyperthermia, caused by regional vasodilation, is induced by extravascular nitric oxide (NO). Extravascular NO can be produced in the affected joint by osteoblasts, chondrocytes, and macrophages, by mechanical stimulation of endothelial cells, or by stimulated neurons. In view of a strong correlation between pain and skin hyperthermia in these disorders, and the evidence that NO enhances the sensitivity of peripheral nociceptors, we also suggest that at least this kind of pain is associated with excessive local level of NO. This hypothesis can be verified by dynamic area telethermometry, assessing the effect of NO on the sympathetic nervous function. This mechanism, which is in line with the general role of NO as a mediator between different organ systems, also may be relevant to any pain associated with enhanced immune response. Clinical implications of the proposed mechanism are discussed.

2. J Oral Maxillofac Surg. 1998 Jul;56(7):872-82; discussion 883-4.
The possible role of nitric oxide in the physiopathology of pain associated with
temporomandibular joint disorders.
Anbar M(1), Gratt BM.
(1)School of Medicine, University at Buffalo, NY 14214-3005, USA.
Temporomandibular joint disorders (TMD) pose a significant challenge to the
practice of oral and maxillofacial surgery. When painful, TMD are generally
associated with hyperthermia of the overlying skin. It is hypothesized that this
skin hyperthermia, caused by regional vasodilation, is induced by nitric oxide
(NO) produced in the extravascular space of the joint. Extravascular NO can be
produced by osteoblasts, chondrocytes and macrophages, or by stimulated neurons.
It is suggested that this kind of pain is associated with NO-enhanced sensitivity
of the peripheral nociceptors. Verification and clinical implications of the
proposed mechanism are discussed.

3. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005 Oct;100(4):441-8.
A pilot study of nitric oxide blood levels in patients with chronic orofacial
pain.
Gratt BM(1), Anbar M.
(1)Department of Oral Medicine, University of Washington, School of Dentistry,
Seattle, WA 98195, USA. [email protected]
BACKGROUND: Control of pain is the major goal in the management of chronic
orofacial pain (COP) patients. The pathogenesis of COP is currently not well
understood. Consequently, the treatment of COP may be suboptimal or even harmful.
Based on independent observations, we propose that local elevated levels of
nitric oxide (NO) may have a central role in the pathogenesis of COP.
HYPOTHESIS: NO level in the orofacial region of COP patients is elevated. A
regional increased level of NO causes excessive vasodilatation. This
hyperperfusion is manifested by hyperthermia of the overlying skin, while NO
enhances nociception, aggravating orofacial pain. An alternative mechanism
involving NO as a neurotransmitter at the CNS level may contribute to orofacial
pain, but seems not to account for all the known clinical observations.
METHODS: Two groups of subjects were studied: 5 patients with COP and 59 control
subjects. For each subject we collected blood samples for analysis of
nitrite\nitrate (or NOx).
RESULTS: (1) NOx blood levels for 5 patients diagnosed with COP was 65.9 microM
(SD of 10.4) verses 42.7 microM (SD of 24.2) for 59 control subjects, the
difference being statistically significant, t-statistic = -2.12 (P > .05). (2) No
statistical difference was found for NOx blood levels for 59 control subjects
divided by gender (male vs female), with 23 female controls having NOx blood
levels of 42.6 microM (SD of 25.2) and male controls having NOx blood levels of
42.8 microM (SD of 24.0), t-statistic = -0.03, P = .98.
CONCLUSION: This pilot study suggests that NO blood levels may have an
association with COP. A better understanding of the mechanism of chronic
orofacial pain is expected to lead to more precise diagnostic staging and
management of this disorder.

Curr Rev Pain. 2000;4(6):459-66.
The role of nitric oxide in nociception.
Luo ZD(1), Cizkova D.
(1)Department of Anesthesiology, University of California, San Diego, 9500 Gilman
Drive, La Jolla, CA 92093-0818, USA. [email protected]
Pharmacologic, electrophysiologic, and immunohistochemical studies have suggested
a role of nitric oxide (NO) in nociception processing. Recent studies have
indicated that NO may modulate spinal and sensory neuron excitability through
multiple mechanisms that may underlie its distinctive roles in different pain
states. Differential regulation of a family of NO-producing enzymes, NO
synthases, contributes mainly to the complexity underlying the role of NO in
nociception. This review summarizes the latest advances in our understanding of
the contribution of NO to pain transduction. Possible cellular mechanisms
regarding the connection between NO production and the abnormal sensation derived
from different stimuli and pathologic conditions are discussed.

Eur J Pharmacol. 2006 Jan 13;530(1-2):59-69. Epub 2005 Dec 20.
Nitric oxide and its modulators in chronic constriction injury-induced
neuropathic pain in rats.
Naik AK(1), Tandan SK, Kumar D, Dudhgaonkar SP.
(1)Division of Pharmacology and Toxicology, Indian Veterinary Research Institute,
Izatnagar.
This study was conducted to examine the role of nitric oxide (NO) in peripheral
neuropathy induced by chronic constriction injury of sciatic nerve of rats by
using NO precursor, NO donors and nitric oxide synthase (NOS) inhibitors. Chronic
constriction injury of sciatic nerve of rats resulted in peripheral neuropathy as
confirmed by nociceptive behavioural tests using mechanical, thermal and cold
allodynia. NO precursor, L-arginine and NO donors sodium nitroprusside,
S-nitroso-N-acetylpenicillamine potentiated the hyperalgesia and allodynia
significantly suggesting proalgesic effect in neuropathic rats.
Intracerebroventricular (i.c.v.) administration of rats with NOS inhibitors such
as L-N(G)-nitroarginine methyl ester, N-iminoethyl lysine and 7-nitroindazole did
not show any effect but i.p. administration of NOS inhibitors aminoguanidine,
L-N(G)-nitroarginine methyl ester and 7-nitroindazole caused alleviation of pain.
The study confirms the involvement of endogenously synthesized and exogenously
administered NO in chronic constriction injury-induced neuropathy in rats.
Significant increase in the levels of nitrate and nitrite in ligated sciatic
nerve suggest that local up regulation of NO in the production and maintenance of
neuropathic pain. In conclusion, initial attempt to manipulate L-arginine: NO
pathway is indicative of therapeutic potential of these interventions in the
management of neuropathic pain.

Cancer Lett. 1994 Aug 29;84(1):23-9.
Hyperthermia of the cancerous breast: analysis of mechanism.
Anbar M(1).
(1)Department of Biophysical Sciences, School of Medicine and Biomedical
Sciences, SUNY, Buffalo 14214.
Cancerous breast hyperthermia is seemingly associated with non-neurological
vasodilation modulated by nitric oxide (NO). NO, associated with enhanced immune
response, is produced autocatalytically involving ferritin as the supplier of
Fe2+, which catalyses the formation of NO. NO, in turn, releases Fe2+ from
ferritin. This mechanism implies: (1) dependence of hyperthermia on the ferritin
content of the neoplastic tissue; (2) oscillatory behavior of the hyperperfusion;
(3) hyperthermia that extends far beyond the boundaries of the neoplastic tissue;
(4) diminished neurological control of the perfusion in the affected breast; (5)
limitations on the observed asymmetry between the breasts. These five effects
were previously observed in numerous independent studies. Monitoring the temporal behavior of the hyperthermia is expected to substantially increase both
sensitivity and specificity of cancer detection.


Curr Med Chem. 2009;16(19):2373-94.
Recent advances on the roles of NO in cancer and chronic inflammatory disorders.
Kanwar JR(1), Kanwar RK, Burrow H, Baratchi S.
(1)Laboratory of Immunology and Molecular Biomedical Research, Centre for
Biotechnology and Interdisciplinary Biosciences (BioDeakin), Institute for
Technology & Research Innovation, Geelong Technology Precinct (GTP), Deakin
University, Pigdons Road, Waurn Ponds, Geelong, Victoria 3217, Australia.
[email protected]
Nitric oxide (NO) is a short-life molecule produced by the enzyme known as the
nitric oxide synthase (NOS), in a reaction that converts arginine and oxygen into
citrulline and NO. There are three isoforms of the enzyme: neuronal NOS (nNOS,
also called NOS1), inducible NOS (iNOS or NOS2), and endothelial NOS (eNOS or
NOS3). It is now known that each of these isoforms may be expressed in a variety
of tissues and cell types. This paper is a review of the current knowledge of
various functions of NO in diseases. We discuss in more detail its role in
Cancer, the role of NO in myocardial pathophysiology, in central nervous system
(CNS) pathologies. Other diseases such as inflammation, asthma, in chronic liver
diseases, inflammatory bowel disease (IBD), arthritis, are also discussed. This
review also covers the role of NO in cardiovascular, central nervous, pancreas,
lung, gut, kidney, myoskeletal and chronic liver diseases (CLD). The ubiquitous
role that the simple gas nitric oxide plays in the body, from maintaining
vascular homeostasis and fighting infections to acting as a neurotransmitter and
its role in cancer, has spurred a lot of interest among researchers all over the
world. Nitric oxide plays an important role in the physiologic modulation of
coronary artery tone and myocardial function. Nitric oxide from iNOS appears to
be a key mediator of such glial-induced neuronal death. The high sensitivity of
neurons to NO is partly due to NO causing inhibition of respiration, rapid
glutamate release from both astrocytes and neurons, and subsequent excitotoxic
death of the neurons.
 

Sucrates

Member
Joined
Jul 20, 2014
Messages
619
Serotonin, histamine and estrogen are all involved too. Estrogen might be the primary driver in some cases. Progest-e might be worth trying. LLLT in the right dose to lower NO, too much could increase it. Lysine, not sure if that could be effective topically.
 

Similar threads

Back
Top Bottom