An Opioid Without Side Effects For Nerve Pain Is That Possible

Today's post is from genengnews.com (see link below). Don't you just love reading an article that contains a sentence like: “Unlike the conventional opioid fentanyl, this agonist showed pH-sensitive binding, heterotrimeric guanine nucleotide–binding protein (G protein) subunit dissociation by fluorescence resonance energy transfer, and adenosine 3′,5′-monophosphate inhibition in vitro.”!! However, with this sort of text, you have to remember that the ordinary neuropathy patient is essentially not the target audience here and this sort of article needs to be read with a sort of 'skim' technique that gives you the gist of what's being said, while skipping over the techno-speak. The article talks about a new form of opioid that is being developed that does the pain-killing job very effectively but doesn't have the side-effects that the media and politicians just can't cope with at the moment. We have to applaud research in the opioid field that doesn't begin with a skull and crossbones declaration that 'all opioids are bad'. Here they are genuinely recognising the benefits of opioids while trying to eliminate the potential harmful side effects. The whole world seems to be searching for opioid alternatives at the moment (powerful lobby - the anti-opioidals!) when the logical thing to search for is opioid adaptations that make them more user-friendly. Worth a read - you'll get the message I promise you.

Opioid Acts Only on Hurt Tissues, Skips Side Effects 
March 6, 2017 Gen News Highlights

  A new opioid can target “disease-specific” (pathological rather than physiological) conformations of receptors and ligands by selectively activating opioid receptors where acidic conditions prevail, as in tissues affected by inflammation or injury. Thus, the opioid brings pain relief at the site of inflammation and does not affect healthy tissues, such as those of the brain or intestinal wall, thereby avoiding side effects. [G. Del Vecchio & V. Spahn/Freepik]

Opioids, like sledgehammers, are powerful but blunt tools. When they are used to flatten pain, opioids may give other things a pounding, too. The problem is conventional opioids act on inflamed or damaged tissues as well as healthy tissues. Consequently, while opioids may relieve pain, they may also cause serious side effects, such as drowsiness, nausea, constipation, and dependency—and in some cases, respiratory arrest.

In hopes of finding a way to craft finer painkilling tools, scientists based at Charité-Universitätsmedizin Berlin scrutinized different ways opioids can interact with opioid receptors. These scientists, led by Prof. Dr. Christoph Stein, were on the lookout for “disease-specific” opioid receptor-ligand conformations. That is, the scientists plan was to exploit pathological (rather than physiological) conformation dynamics in the design of new opioids, and thereby create drugs that would target damaged or inflamed tissues yet bypass healthy tissues.

"By analyzing drug–opioid receptor interactions in damaged tissues, as opposed to healthy tissues, we were hoping to provide useful information for the design of new painkillers without harmful side effects," said Prof. Dr. Stein.

Prof. Dr. Stein’s team was aware that previous strategies in drug development had focused on central opioid receptors in noninjured environments, even though many painful syndromes (such as arthritis, neuropathy, and surgery) are driven by peripheral sensory neurons and are typically accompanied by inflammation with tissue acidosis. Ultimately, the team decided that this alternative mechanism of action—the binding and activation of peripheral opioid receptors—could be preferentially exploited by a new class of opioids. The key was the occurrence of acid conditions.

By following through on this idea, the scientists designed a new opioid that, unlike clinically used opioids, best activates the receptors in acidified tissues. When the new opioid was evaluated in a rat model of inflammatory pain, it exerted strong pain relief essentially without the side effects of standard opioids.

Details appeared March 3 in the journal Science, in an article entitled, “A Nontoxic Pain Killer Designed by Modeling of Pathological Receptor Conformations.” The article describes how the scientists used computer modeling to analyze morphine-like molecules and their interactions with opioid receptors. In particular, computer modeling was used to simulate an increased concentration of protons, thereby mimicking the acidic conditions found in inflamed tissues.

“By computer simulations at low pH, a hallmark of injured tissue, we designed an agonist that, because of its low acid dissociation constant, selectively activates peripheral μ-opioid receptors at the source of pain generation,” wrote the article’s authors. “Unlike the conventional opioid fentanyl, this agonist showed pH-sensitive binding, heterotrimeric guanine nucleotide–binding protein (G protein) subunit dissociation by fluorescence resonance energy transfer, and adenosine 3′,5′-monophosphate inhibition in vitro.”

The authors observed that their novel opioid produced injury-restricted analgesia in rats with different types of inflammatory pain without exhibiting respiratory depression, sedation, constipation, or addiction potential. These results, the authors suggested, mean that treating postoperative and chronic inflammatory pain should now be possible without causing side effects. Doing so would substantially improve patient quality of life.

“In contrast to conventional opioids, our NFEPP-prototype appears to only bind to, and activate, opioid receptors in an acidic environment,” explained the study's first authors, Dr. Viola Spahn and Dr. Giovanna Del Vecchio. “This means it produces pain relief only in injured tissues, and without causing respiratory depression, drowsiness, the risk of dependency, or constipation."

"We were able to show that the protonation of drugs is a key requirement for the activation of opioid receptors," the authors concluded. Their findings, which may also apply to other types of pain, may even find application in other areas of receptor research. Thereby, the benefits of improved drug efficacy and tolerability are not limited to painkillers, but may include other drugs as well.

http://www.genengnews.com/gen-news-highlights/opioid-acts-only-on-hurt-tissues-skips-side-effects/81253978

Fifty Eight Possible Causes Of Neuropathy

Today's post from symptoms.rightdiagnosis.com (see link below) is guaranteed to frighten the life out of you if you have neuropathic symptoms but are not sure where they come from. Most people are aware that there are over 100 causes of neuropathy, so take your pick from this list of 58. However, the cause of your neuropathy most likely comes  from just one source, with the possibility of one or two more to complicate the picture (for instance, HIV plus diabetes plus alcoholism) depending on your health history. Your doctor or specialist should be able to pin point the most likely cause but remember, finding the cause is not as important as treating the symptoms you now have. They will be very similar to those people who have neuropathy from other diseases but the treatments are much the same for everybody. This is an interesting list with lots of useful links to further information but perhaps not for those with a tendency towards hypochondria! - always seek expert advice and assume nothing.

58 causes of Neuropathic manifestations of HIV infection OR Foot ulcer

Symptom Checker

1. Alcoholism
Alcoholism is the compulsive urge to drink alcohol despite knowing the negative impact on one's health....more »

2. Atherosclerosis
Atherosclerosis is a syndrome affecting arterial blood vessels. It is a chronic inflammatory response in the walls of arteries, in large part due to the accumulation of macrophage white blood cells and promoted by low density (especially small particle) l...more »

3. Bedsores
Skin ulcers from prolonged pressure...more »

4. Blastomycosis
A fungal infection caused by Blastomyces dermatitidis and resulting in lung, skin, bone and genitourinary involvement....more »

5. Buerger's disease
Buergers's disease is a recurring inflammation and thrombosis (clotting) of small and medium arteries and veins of the hands and feet...more »

6. Cancer
Abnormal overgrowth of body cells....more »

7. Cervical hypertrichosis -- peripheral neuropathy
A rare genetic disorder characterized by excessive body hair at birth and peripheral neuropathy....more »

8. Charcot-Marie-Tooth disease, Type 2B
CMT is an inherited neurological disease characterized by the gradual degeneration of nerves which starts in the hands and feet and results in progressive numbness, muscle weakness and loss of function. Type 2B has an autosomal dominant inheritance and in...more »

9. Charcot-Marie-Tooth disease, Type 4F
CMT is an inherited neurological disease characterized by the gradual degeneration of nerves which starts in the hands and feet and results in progressive numbness, muscle weakness and loss of function. Type 4F has an autosomal recessive form of inheritan...more »

10. Diabetes Mellitus, Insulin-Dependent, Susceptibility to, 1
Insulin-dependent diabetes is a condition where the body is unable to produce its own insulin in sufficient quantities to regulate blood sugar levels. Researchers have discovered a number of genes which are linked to an increased risk of developing type 1...more »

11. Diabetes Mellitus, Insulin-Dependent, Susceptibility to, 10
Insulin-dependent diabetes is a condition where the body is unable to produce its own insulin in sufficient quantities to regulate blood sugar levels. Researchers have discovered a number of genes which are linked to an increased risk of developing type 1...more »

12. Diabetes Mellitus, Insulin-Dependent, Susceptibility to, 11
Insulin-dependent diabetes is a condition where the body is unable to produce its own insulin in sufficient quantities to regulate blood sugar levels. Researchers have discovered a number of genes which are linked to an increased risk of developing type 1...more »

13. Diabetes Mellitus, Insulin-Dependent, Susceptibility to, 12
Insulin-dependent diabetes is a condition where the body is unable to produce its own insulin in sufficient quantities to regulate blood sugar levels. Researchers have discovered a number of genes which are linked to an increased risk of developing type 1...more »

14. Diabetes Mellitus, Insulin-Dependent, Susceptibility to, 13
Insulin-dependent diabetes is a condition where the body is unable to produce its own insulin in sufficient quantities to regulate blood sugar levels. Researchers have discovered a number of genes which are linked to an increased risk of developing type 1...more »

15. Diabetes Mellitus, Insulin-Dependent, Susceptibility to, 15
Insulin-dependent diabetes is a condition where the body is unable to produce its own insulin in sufficient quantities to regulate blood sugar levels. Researchers have discovered a number of genes which are linked to an increased risk of developing type 1...more »

16. Diabetes Mellitus, Insulin-Dependent, Susceptibility to, 17
Insulin-dependent diabetes is a condition where the body is unable to produce its own insulin in sufficient quantities to regulate blood sugar levels. Researchers have discovered a number of genes which are linked to an increased risk of developing type 1...more »

17. Diabetes Mellitus, Insulin-Dependent, Susceptibility to, 18
Insulin-dependent diabetes is a condition where the body is unable to produce its own insulin in sufficient quantities to regulate blood sugar levels. Researchers have discovered a number of genes which are linked to an increased risk of developing type 1...more »

18. Diabetes Mellitus, Insulin-Dependent, Susceptibility to, 19
Insulin-dependent diabetes is a condition where the body is unable to produce its own insulin in sufficient quantities to regulate blood sugar levels. Researchers have discovered a number of genes which are linked to an increased risk of developing type 1...more »

19. Diabetes Mellitus, Insulin-Dependent, Susceptibility to, 2
Insulin-dependent diabetes is a condition where the body is unable to produce its own insulin in sufficient quantities to regulate blood sugar levels. Researchers have discovered a number of genes which are linked to an increased risk of developing type 1...more »

20. Diabetes Mellitus, Insulin-Dependent, Susceptibility to, 20
Insulin-dependent diabetes is a condition where the body is unable to produce its own insulin in sufficient quantities to regulate blood sugar levels. Researchers have discovered a number of genes which are linked to an increased risk of developing type 1...more »

21. Diabetes Mellitus, Insulin-Dependent, Susceptibility to, 21
Insulin-dependent diabetes is a condition where the body is unable to produce its own insulin in sufficient quantities to regulate blood sugar levels. Researchers have discovered a number of genes which are linked to an increased risk of developing type 1...more »

22. Diabetes Mellitus, Insulin-Dependent, Susceptibility to, 22
Insulin-dependent diabetes is a condition where the body is unable to produce its own insulin in sufficient quantities to regulate blood sugar levels. Researchers have discovered a number of genes which are linked to an increased risk of developing type 1...more »

23. Diabetes Mellitus, Insulin-Dependent, Susceptibility to, 23
Insulin-dependent diabetes is a condition where the body is unable to produce its own insulin in sufficient quantities to regulate blood sugar levels. Researchers have discovered a number of genes which are linked to an increased risk of developing type 1...more »

24. Diabetes Mellitus, Insulin-Dependent, Susceptibility to, 24
Insulin-dependent diabetes is a condition where the body is unable to produce its own insulin in sufficient quantities to regulate blood sugar levels. Researchers have discovered a number of genes which are linked to an increased risk of developing type 1...more »

25. Diabetes Mellitus, Insulin-Dependent, Susceptibility to, 3
Insulin-dependent diabetes is a condition where the body is unable to produce its own insulin in sufficient quantities to regulate blood sugar levels. Researchers have discovered a number of genes which are linked to an increased risk of developing type 1...more »

26. Diabetes Mellitus, Insulin-Dependent, Susceptibility to, 4
Insulin-dependent diabetes is a condition where the body is unable to produce its own insulin in sufficient quantities to regulate blood sugar levels. Researchers have discovered a number of genes which are linked to an increased risk of developing type 1...more »

27. Diabetes Mellitus, Insulin-Dependent, Susceptibility to, 5
Insulin-dependent diabetes is a condition where the body is unable to produce its own insulin in sufficient quantities to regulate blood sugar levels. Researchers have discovered a number of genes which are linked to an increased risk of developing type 1...more »

28. Diabetes Mellitus, Insulin-Dependent, Susceptibility to, 6
Insulin-dependent diabetes is a condition where the body is unable to produce its own insulin in sufficient quantities to regulate blood sugar levels. Researchers have discovered a number of genes which are linked to an increased risk of developing type 1...more »

29. Diabetes Mellitus, Insulin-Dependent, Susceptibility to, 7
Insulin-dependent diabetes is a condition where the body is unable to produce its own insulin in sufficient quantities to regulate blood sugar levels. Researchers have discovered a number of genes which are linked to an increased risk of developing type 1...more »
30. Diabetes Mellitus, Insulin-Dependent, Susceptibility to, 8
Insulin-dependent diabetes is a condition where the body is unable to produce its own insulin in sufficient quantities to regulate blood sugar levels. Researchers have discovered a number of genes which are linked to an increased risk of developing type 1...more »

31. Familial amyloid polyneuropathy
A rare inherited condition where impaired nerve function is caused by amyloid deposits in peripheral nerves....more »

32. Fitzsimmons-Guilbert syndrome
A very rare syndrome characterized mainly by paraplegia, short fingers and bone abnormalities. The paraplegia progresses slowly....more »

33. Foot injury
Any injury to the foot...more »

34. Fungal infections
Any condition caused by fungus....more »

35. Headache
In medicine a headache or cephalalgia is a symptom of a number of different conditions of the head and sometimes neck. Some of the causes are benign while others are medical emergencies. It ranks among the most common pain complaints...more »

36. Ischemia
Inadequate blood supply to tissues, usually caused by a problem in the blood vessel....more »

37. Leprosy
A chronic, progressive infectious disease caused by Mycobacterium leprae which causes skin sores and also affects the eyes, mucous membranes and peripheral nerves....more »

38. Motor and Sensory Neuropathy with Sensorineural Hearing Loss, Bouldin type
A rare condition observed in two sibling and characterized by hearing loss during adulthood and motor and sensory neuropathy....more »

39. Neuropathy ataxia and retinis pigmentosa
A rare inherited disorder where defects in the energy producing part of cells affects the nervous system and causes symptoms such as muscle and vision problems. Severity and rang of symptoms are variable....more »

40. Neuropathy sensory spastic paraplegia
A very rare syndrome characterized mainly by sensory nerve degeneration and spastic paraplegia. The extremities of the hands and feet have reduced pain sensation and disfiguring ulcers tend to develop....more »

41. Neuropathy, Hereditary Sensory and Autonomic Type I
Type I hereditary sensory neuropathy is an inherited condition characterized by progressive degeneration of the nervous system which manifests primarily as loss of sensation in the hands and feet. The sensory loss is worse in the feet and legs than the ha...more »

42. Neuropathy, Hereditary Sensory, Type I
Type I hereditary sensory neuropathy is an inherited condition characterized by progressive degeneration of the nervous system which manifests primarily as loss of sensation in the hands and feet. The sensory loss is worse in the feet and legs than the ha...more »

43. Neuropathy, hereditary, sensory, radicular
A rare inherited degenerative disorder of the nervous system characterized by sensory loss in limbs, pain and foot ulcers....more »

44. Parsonage Turner syndrome
Inflammation of the nerves that carry signals from the spine to the shoulder, arm and hands....more »

45. Peripheral neuropathy
Peripheral neuropathy is the term for damage to nerves of the peripheral nervous system, which may be caused either by diseases of the nerve or from the side-effects of systemic illness....more »

46. Portuguese type amyloidosis
An inherited form of systemic amyloidosis which involves deposits of a substance called amyloid throughout various parts of the body....more »

47. Radiculopathy
A condition characterized by disease of the nerve roots...more »

48. Raynaud's phenomenon
Blood vessel constriction attacks affecting fingers and/or toes....more »

49. Sensory neuropathy type 1
Type I sensory neuropathy is an inherited condition characterized by progressive degeneration of the nervous system which manifests primarily as loss of sensation in the hands and feet. The sensory loss is worse in the feet and legs than the hands and arm...more »

50. Sickle Cell Anemia
Sickle cell anemia is an inherited blood disorder characterized by red blood cells which are crescent-shaped rather than the normal doughnut shape. These abnormally shaped red blood cells are unable to function normally and tend to undergo premature destr...more »

51. Sporotrichosis
A fungal skin infection caused by the fungus Sporothrix schenckii. Usually only the skin is infected but bones, lungs and central nervous system can rarely be affected also. Transmission usually occurs through infection of a skin wound....more »

52. Tumor
Any type of lump or swelling (not just cancers)...more »

53. Type 1 diabetes
Severe insulin-treated diabetes typically occurring in young people....more »

54. Type 2 diabetes
Most common diabetes in adults, usually progressing slowly, mostly treated without insulin at diagnosis....more »

55. Type IV Hyperlipoproteinemia
Type IV Hyperlipoproteinemia is an inherited condition characterized by high levels of very low density lipoproteins (VLDL) in the blood which in turn causes high cholesterol levels. Lipoproteins are responsible for transporting cholesterol in the bloodst...more »

56. Venous Insufficiency
A condition where the valves in the leg veins are unable to pump blood to the heart which causes blood to pool below the defective valves....more »

57. Werner syndrome
A form of premature aging where sufferers start aging during adolescence or soon after and appear old by the time they reach their 30's or 40's. Milder forms of the condition may also occur....more »

58. Woodhouse Sakati syndrome
A condition which consists of numerous symptoms such as diabetes, hypogonadism, deafness and mental retardation...more 

http://symptoms.rightdiagnosis.com/cosymptoms/neuropathic-manifestations-of-hiv-infection/foot-ulcer-desc-sall.htm