Neuropharmacognosy: is it nature’s answer for neuropathy?
Neuropathy literally means diseased nerves. There are a number of different reasons why people develop neuropathy. Very commonly, neuropathy is associated with diabetes, vitamin deficiencies, inflammation of the nerves, and toxins that poison the nerves. We have discussed many of the conditions that cause nerve disease in patients in other articles. Patients suffering from the signs and symptoms of neuropathy experience pain, burning, numbness and other strange sensations known as paresthesias that most often begin in the feet and progress throughout the rest of the body. Pain and other symptoms can be debilitating and disabling, regardless of the reason for the neuropathy.
The nervous system in higher animals like humans is a highly complex collection of specialized cells known as neurons. Neurons have several unique features, including a wire-like process known as an axon. The axon works much like an electrical wire and carries coded electrical signals known as nerve impulses throughout the body. Like a copper wire, the nerve axon has insulation around it known as myelin. Unlike a copper wire, a nerve cell and its wirelike axon is living tissue. The neuron contains all the cellular machinery necessary to produce energy, maintain itself, and generate energy to support its function of transmitting and receiving electrical signals. Each neuron is an electrochemical marvel and is essentially a living battery. This amazing communication network occurs at the microscopic level and consumes incredible amounts of energy to function properly.
The myelin insulation surrounding the nerve axon is also living tissue and the nerve cell and its associated myelin cells are intimately arranged to maintain and support each other.
The nervous system typically does a remarkable job of sending and receiving information from various parts of the body, acting both as a sensor system to monitor what is happening in the body and as an effector system that drives necessary changes in the body based on sensor input.
Due to its complexity, the nervous system and the myelin cells that support it are vulnerable to the slightest disturbance of metabolism. Axons are like a microscopic spider web but travel great distances within the body. They can be very easily deregulated by trauma or compression.
Think of the nervous system as a living, delicate, and vulnerable communications network that consumes extraordinary amounts of energy to function and maintain itself. Not surprisingly, the nervous system is susceptible to injury, disease, metabolic abnormalities, immune problems, and many other afflictions that can make it sick and malfunction.
Peripheral nervous system malfunction occurs frequently and when this happens, people develop the cardinal symptoms of polyneuropathy.
Although polyneuropathy is one of the most common diseases of the peripheral nervous system, there are few FDA-approved medications available to treat it. Many patients who try traditional prescription drugs to relieve their neuropathy symptoms are disappointed with the results.
Too often, the newest drugs in the pipeline look promising but fail due to unwanted side effects. Research and data obtained from failed drug development experiments can sometimes be applied to herbal medicine where natural substances can work similarly to man-made chemicals, but with less severe side effects. The scientific study of natural substances that can mimic artificial drugs is known as Pharmacognosy. When this knowledge is applied to the nervous system we call it Neuropharmacognosy. You can translate this as the study of the pharmacology of natural substances that can influence the function of the nervous system. There are a number of natural substances that can mimic the pharmacology of drugs used to treat neuropathy. We’ve discussed them in other articles, but we’ll review them together here.
Based on experimental data on nerve function and disease, a number of broad classes of chemicals may have theoretical application in alleviating symptoms of neuropathy.
It seems that when nerves become diseased, raising a chemical known as GABA can calm irritable and inflamed nerves and bring relief to people struggling with symptoms of neuropathy. You can think of GABA as a brake pedal that slows down the symptoms of neuropathy. There is research to suggest that the herbs, valerian root and lemon balm, can increase GABA, thereby putting the body’s brakes on uncontrolled nerve pain. Valerian root can block an enzyme known as GABA-T that breaks down and neutralizes GABA in the nervous system. By blocking the breakdown of GABA, valerian root can prolong the braking effect of GABA on the nerve and slow down the symptoms of neuropathy. Lemon Balm seems to increase the effect of GABA in a slightly different way. Instead of blocking the breakdown of GABA, Lemon Balm can stimulate an enzyme known as GAD, which is responsible for building GABA. So, the stopping action of GABA in the diseased nerve is supported by the increased production of this neurotransmitter.
If GABA acts as the body’s brake on a runaway nervous system, glutamate is the nerve’s accelerator. Studies suggest that injured nerves become hypersensitive because glutamate is released after the nervous system is irritated. This has the effect of sensitizing the nerve and contributing to the signs and symptoms of neuropathy. There are two potentially important herbs that can block the effects of glutamate on the nervous system in neuropathy. The first is theanine, a protein derived from green tea. Theanine is believed to act as a glutamate analogue. This means that theanine is processed by the body like glutamate, but does not have the nerve-stimulating effects of glutamate. Think of Theanine as a blank bullet that has the net effect of reducing the actions of glutamate. The other herb that can reduce the excitatory effects of glutamate is magnolia bark. Magnolia Bark is believed to bind to a specific glutamate receptor and block it. This suggests that Magnolia Bark is a specific glutamate antagonist and could be a more targeted way of taking the foot off the gas on nerves damaged by neuropathy.
In keeping with our car analogy, if GABA is the nerve brake in neuropathy and glutamate acts as the accelerator, a third chemical known as glycine could be considered to be the transmission. Glycine slows down the nervous system. Think about putting the nerve in low gear. Glycine reduces the nerve in neuropathy directly, which slows down and inhibits the painful transmission of nerve signals, but it can also compete indirectly with glutamate. The mechanism by which glycine might bring relief to patients suffering from neuropathy is a little less straightforward. If a patient were to take a large dose of Glycine, the nerves would slow down. However, this effect would not last long, because in the nervous system, glycine is transported out of the nerve by what is known as the glycine transporter. The glycine transporter has the net effect of getting rid of the glycine, which gets the nervous system back into full gear. This glycine transport system is so effective that it makes glycine an impractical treatment for neuropathy. Due to the glycine transporter, the nerve simply cannot keep enough glycine in the nerve to slow down the function of a hypersensitive nerve significantly. However, there are substances that can inhibit the glycine transporter and this appears to be a promising way to enhance the suppression of nerve hyperexcitability such as occurs in neuropathy. The herb Prickly Ash Bark appears to be an important inhibitor of the glycine transporter. Prickly Ash has a long history of use for pain relief. Also, the natural compound sarcosine is a known inhibitor of the glycine transporter. Both naturally occurring substances appear to be candidates for the relief of signs and symptoms of neuropathy.
Another pathway that can be exploited for the relief of neuropathy is the endogenous cannabinoid receptor system. This system is activated by marijuana and is believed to suppress pain at the highest levels of the nervous system. Endogenous cannabinoid system receptors can be activated to relieve pain without producing the “high” and side effects associated with marijuana drug use by certain fatty acid breakdown products in the nervous system. Substances that block the enzyme fatty acid amide hydrolase or FAAH appear to activate the endogenous cannabinoid system and are currently being investigated for the treatment of neuropathic pain. There appear to be natural FAAH inhibitors in Red Clover and the herb MACA. This suggests that these herbs through their potential to modulate FAAH enzyme activity may be able to activate the endogenous cannabinoid system and provide relief from neuropathic pain.
Finally, with particular reference to neuropathy associated with diabetes, the protein kinase C or PKC enzyme and its relationship to T-type calcium channels may be therapeutic targets. It appears that elevated blood glucose does not regulate PKC in diabetic nerves. PKC appears to drive specific calcium channels in diabetic nerves known as T-type calcium channels. These changes are thought to drive hypersensitivity and excitability at least in nerves affected by diabetic neuropathy.
Chelidonium Majus is an herbal remedy that can modulate PKC. The chelerythrine alkaloid found in this herb is a potent protein kinase C antagonist. This suggests a possible benefit of this herb in polyneuropathy. Although generally safe, some reports of liver toxicity associated with Chelidonium Majus appear in the medical literature.
Picrorhiza Kurroa is an herb that contains the phytochemical Apocynin. At least one study suggests that apocynin prevented or markedly reduced the upregulation of T-type calcium channels Cav3.1 and Cav3.2. This suggests that Picrorhiza Kurroa may downregulate overexpression of T-type Cav3.2 calcium channels that are thought to contribute to the hyperexcitability of nerves seen in diabetic neuropathy.
One final note and warning about using information from the Internet to try to treat a medical condition. Do not do it! The use of this article is provided solely for patients to discuss the information contained with their licensed healthcare provider. Herbal treatments, while generally safe, can have unwanted or unpredictable side effects. Only a licensed physician who is familiar with your specific medical condition can safely diagnose you and advise you on treatment for your particular condition. Always consult and inform your doctor before making any additions or changes to your treatment regimen.