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October 2013 UPDATE

There are three drugs that I have injected around nerves for nerve pain that have produced consistently beneficial effects in the majority of patients. Although prescribed for other disorders, their use in pain relief is largely unrecognized. I review my experience with them, and some others, below, in the hope of encouraging their more widespread use.

HEPARIN

Easily available, inexpensive, and small amounts placed close to to an irritated, painful nerve often produce dramatic pain relief. This involves injections described in "Lecture on Treatment" and "Heparin alleviates pain" paper in "Bibliographies" on this website. These injections consistently produce more than 50% pain relief, but, in severe cases, last only two to three weeks, requiring re-treatment. This is an obvious draw back, but patients are very willing to undergo repeated injections because nothing else that they've tried works as well.

Over the last twenty years, I've treated close to 500 patients with nerve entrapments, many for long periods of time, with no side effects other than bruising at the site of injection. I attribute this to the small doses, intervals of at least two weeks between injections, and the otherwise decent health of my patient population.

Anecdotally, Heparin has relieved pain in multiple other disorders (see "Innervated Fibrosis" front page this web site), most notably, at my hands, that of chronic low back pain in individuals with diabetic neuropathy as well as a few women with moderate endometriosis.

See my paper and "Heparin' in "Bibliographies" for more information.

ERYTHROPOIETIN

Erythropoietin (Epo) has a number of beneficial effects besides stimulating blood formation, one of which is neuroprotection. It protects by normalizing aberrant nerve function, an aspect of which is pain control, providing nuclear changes and more lasting pain relief than that obtained by Heparin. It is delivered locally by injection in the same manner as described above for Heparin.

Over thirty patients with nerve entrapments have now been treated with a course of six treatments given once every rwo weeks for six weeks and continue to show excellent pain relief. Improvement is incremental, often not noticed for several days, but lasting indefinitely or until serious re-injury. Very severe patients have needed ongoing treatment every one to two months, but the majority has been pleased obtaining 80-100% pain relief albeit with some continued sensitivity to re-injury- a common problem.

So far, side effects have been restricted to one episode of hypertension, resolved with no consequences in 24 hours. Small doses, large time intervals, and generally decent health minimize the possibility of blood clots- a recognized potential side effect-although occurring in a very different context. The relief has been felt to be worth the risk. Given my patient population, the major draw-back is price. Epo adds about $100 to the cost of each treatment, uncovered by insurance.

VASOACTIVE INTESTINAL PEPTIDE

Vasoactive Intestinal Peptide (VIP) is a pleiotropic molecule produced in most of our tissues with clear cut neuroprotective properties. I first used VIP some time ago when investigating the effects of a number of different neuropeptides on varieties of chronic pain and found VIP to be dramatically effective in very small concentrations in treating painful, hypersensitized (hyperesthesia and allodynia) skin topically. This led to an experimental protocol to test its effectiveness in patients with RSD/CRPS and nerve entrapments approved by the EOB at UCSF but sadly never realized. I did gain the approval of a major EOB as to the reasonableness of my ideas.

Having been fortunate in obtaining a small stock of VIP for the potential UCSF study, I was subsequently able to use it as a wound healing agent in two other, unrelated disorders to good effect. This re-invigorated by interest and I applied the UCSF protocol to eight patients with chronic, severe, Thoracic Outlet Syndrome. Seven patients reported dramatic lessening of pain (80-100%) in 3-24 hrs. This relief, however, was highly variable in how long it lasted- from three hours to one year and counting. Six patients had incremental improvement with every treatment (once every other week for four treatments) arguing for a cumulative effect with the obvious and necessary question of what is the optimal number of treatments? They continue to show improvement compared to pre-VIP with two patients continuing pain free.

Interestingly, three patients spontaneously reported intense well-being, oceanic, non-sexual, interactive, lasting for one to two days. The other four responders remarked that the dramatically lessened or now absent pain was more than enough to feel "real good".

Of the three substances I have found to work in relieving nerve entrapments (and probably many other neuropathic pain disorders), Heparin, Epo, and VIP, VIP is the most impressive for the speed and extent of its pain relief. Many questions regarding placement, dosage and timing remain. Thankfully, no side effects were reported.

The only draw-back currently is availabilty. VIP is dispensed as injectable medication for erectile dysfunction in England and New Zealand. Here, in the States, it's only available from specialty chemical manufacturers as a substance for experimental use. This takes time, money (raw manufacturing costs at Sigma are about $500 per treatment dose), and an encouraging environment.

VIP, admittedly in very small samples, is effective in reducing and then eliminating the pain and hyperreactiveness of skin in patients with CRPS/RSD, and improving substantially, even eliminating severe neuropathic symptoms all with no side-effects. Given its wide spread physiological effects, VIP might be of significant benefit in most disorders needing wound healing or tissue function normalization. I predict its spectrum of treatment to be wider than that for Epo (see above).

OTHER DRUGS

Diazepam continues to be a first choice with its neuroprotection and striated muscle relaxation.

Of the opiates I prefer to use Nalbuphine when possible because it has proven consistently more effective in entrapment disorders than even Fentanyl.

Anti epileptics, especially Gabapentin and congeners, can be of significant benefit mainly limited by side-effects.

Nitroglycerine as a patch can be very effective for foci of neuropathic pain, limited here by the occurrence of headache.

Pentoxifyllene is turning out to be another symptom relieving drug with little side effects and a pleasing reduction in pain without sedation. Patients report a 10-30% reduction in symptoms. Other vaso-active agents such as Fasudil might become available in the future.

SO WHAT

So what is that all the stuff I've brought up about old drugs used in new ways and for different disorders gives hope. It says that even though pain and human disease continue to be largely the proverbial black boxes, we can still find new ways of making people feel better. This is of primary importance when trying to understand and negotiate the bottleneck of voluminous research with little to show for it clinically. We have not been barking up the right tree(s) for pain mechanisms and their control when substances that sequester cytokines (Heparin), induce neural maturation (Epo), or set off multiple cAMP cascades(VIP) can all affectively neutralize chronic pain.

My own best guess is that the basic intraneuronal mechanism allowing pain as a signal involves phase changes in endoplasmic reticulum tethered microtubular arrays, otherwise involved in non-pathological signalling. We'll see.