By Robert W. Bastian, MD

People with sensory neuropathic cough often spend years searching in vain for a correct diagnosis and effective treatment. In a group of 110 consecutive patients diagnosed with sensory neuropathic cough by the author in 2005, the median duration of cough prior to diagnosis was 10 years, ranging from a few weeks to 62 years.

Such individuals will first visit their own primary care physician, and then an allergist, pulmonologist, gastroenterologist, and otolaryngologist. In each place, he or she may submit to a long list of tests, such as chest x-ray, various scans of the chest or sinuses, pulmonary function tests, allergy tests, bronchoscopy, esophagoscopy, 24-hour pH probe, and so forth. These tests are done to evaluate some “usual suspects,” for chronic cough—in particular, allergy, acid reflux, and cough-variant asthma.

Add to all of this that an individual with sensory neuropathic cough may have tried several to dozens of medications, including antihistamines, asthma inhalers, acid suppressors, antibiotics, cough suppressants, expectorants, and steroids—even when testing for the conditions for which those medications are used was negative. This leaves medicine chests cluttered with bottles of drugs that did not work.

The record for most grueling diagnosis search in my experience was an out-of-state patient who had been coughing for 16 years—she had seen more than 20 different physicians, undergone countless tests, and had tried 40 different medications. Her cough was the same or worse than at the beginning. After all of this time, effort, and money had been expended, with zero benefit, such a patient would understandably and reasonably be skeptical and even medically jaded, perhaps to the point of not actually complying (either overtly or covertly) with a new suggested treatment regimen.

On the other hand, the physician has not participated in the patient’s prior travails and instead may be focused on his or her previous treatment success with neuralgia medications. If the physician does not grasp the depth of the patient’s prior disappointments, he or she may not recognize when the patient is by appearances cordial and respectful, but is actually in great doubt about this “new” diagnosis.

Patient 1: Medically jaded but cordial
Several years ago, a middle-aged woman many years into an unsuccessful search for a correct diagnosis for her chronic cough came for a consultation, having heard of our work. Her history was classic for the syndrome of sensory neuropathic cough.¹ I educated her extensively and also had her watch a comprehensive teaching video we use to reinforce the nature of the diagnosis and explain the strategy for testing one or more neuralgia medications. She left the office with a prescription for amitriptyline and what we call our “roadmap,” detailing in a third format the strategy, voicemail instructions, and the six things we want to know when patients phone the office to give a status report and request further instructions.

Several weeks went by, and we didn’t hear from her. I believe we tried to contact her several months later, but our voicemail did not elicit a return call. Two years later, she reappeared on my schedule. After exchanging initial greetings, I said, “I notice that we have no information about your response to the first medication you tried, amitriptyline. Did your cough go away?”

No,” she said, “The amitriptyline did nothing, and I stopped it. The cough has been as bad as ever these past two years, and I’m ready to try your second medicine.”

“Why,” I asked, “didn’t you try it two years ago?”

She said, “Well doctor, I had already seen so many doctors, and tried so many things that when your first medicine didn’t work… I just blew you off.” She still seemed to me war-weary and uninspired about my diagnosis. Happily, the second medication, gabapentin, worked extremely well for her. I was struck to think that she had coughed aggressively, almost to the point of debilitation, needlessly, for two years.

Patient 2: Hostile and even contemptuous
Out of the flow of hundreds of patients across many years, one encounter stands out vividly. I entered the examination room to meet a new patient, a nurse in her 40s. The instant I entered the room, I sensed remarkably tangible hostility. I remember thinking for a moment that I must be two hours late, though I knew I was actually running nearly on time. Through the frost, I reviewed the story of her classic but as-yet undiagnosed sensory neuropathic cough. I spent more time than usual with her, trying to find common ground and thaw the ice. I spent more time that was necessary for my benefit on the details of prior evaluations, tests, and unsuccessful treatments.

Well into the consultation and after examination, I introduced her to the diagnosis. Sensing her skepticism, I explained with analogy after analogy the concept of sensory neuropathy causing not pain, but instead, the tickling sensation that initiated each of her coughing attacks. I suggested beginning with amitriptyline. She accepted the prescription and departed. I felt drained, thinking the entire encounter was a failure and that it would likely be my last with her.

The encounter had been so unpleasant that I remembered the name when it appeared on my schedule two weeks later. I strapped on a figurative suit of armor and consciously decided that I would be cordial but not work as hard this time around. I entered the room with my guard up. To my surprise, the atmosphere in the room was dramatically different. It was as though the sun was shining; the ice was melted. The patient’s face was strikingly transformed.

Even so, I sat down tentatively. “You were just here two weeks ago,” I said. “Is there something else we need to discuss?”

“Dr. Bastian,” she said, smiling, “I am not here for any medical reason. I made this appointment purely to apologize to you.” She went on, “You have to understand that when I saw you, I had been everywhere and done everything. I had gone to major national centers. Then I came here and you gave me this new diagnosis and I said to myself, ‘Right, another bright idea that will go nowhere.’”

She went on to say that her response to amitriptyline hadn’t yet abolished her cough, but it had been reduced to an amazing degree. She was simply thrilled.

The physician must bear the brunt
It is completely understandable for patients with sensory neuropathic cough to become cynical and feel that the medical profession has failed them. We can know that collectively the many prior physicians have worked very hard within existing paradigms, and we can also explain to ourselves and to the patient that physicians cannot diagnose what they do not know about. Nevertheless, it is up to us to compensate for the patients’ medical jadedness.

Here are a few ways that we as physicians can help the patient:

1. Acknowledge the patient’s prior experience. I can imagine that you are exhausted, and skeptical by now of each new idea. But I want you to bear with me while I explain something you may not have heard of before.
2. Stress that you want the patient to join you in a process that may take some weeks or months to complete. I really want to start you on a path that I believe can bring you some considerable relief. You might see some benefit from the first medicine, and within the first few days. But many who eventually get wonderful benefit don’t see that benefit until they try medication 2 or 3. Trying two or three different medications in sequence can take some weeks, and a lot of patience. Please do not give up. We sometimes say around here that you can’t give up unless I give up (and I never give up).
3. Show good faith by your generosity of effort. It can take some back and forth communication between you and me to get to the best medication for you. We have prepared a sheet to help you do your part. We have listed voicemail instructions and also the six things we want to know from you, every time you call the office. We do it this way to spare you trips back and forth to the office.
4. Set up a careful protocol with office staff to get messages back and forth, and prescriptions filled and refilled expeditiously. This conveys to patients the importance with which you take their dreadful problem.

The rewards are great
Patients with sensory neuropathic cough do not die. But, especially if the disorder is severe, their lives can be practically ruined. Until recently sensory neuropathic cough has been an orphan disorder, and patients with it, orphans in the medical community. Although it can be labor-intensive to work through the process of finding best treatment, going through numerous calls back and forth between patient and physician, with office staff as the hard-working go-between—working with this group of patients is extraordinarily gratifying.

References:

Bastian ZJ, Bastian RW. (2015) The use of neuralgia medications to treat sensory neuropathic cough: our experience in a retrospective cohort of thirty-two patients. PeerJ 3:e816 https://dx.doi.org/10.7717/peerj.816

1. Bastian RW, Vaidya AM, Delsupehe KG. Sensory neuropathic cough: a common and treatable cause of chronic cough. Otolaryngol Head and Neck Surg. 2006; 135(1): 17-21. ↩

By Robert W. Bastian, MD

In recent years, a neurogenic form of chronic cough has been described in the literature, referred to variously as “sensory neuropathy presenting as chronic cough”¹, “sensory neuropathic cough”^2,3, “laryngeal sensory neuropathy”⁴, or simply “refractory chronic cough”⁵. It has been shown that sensory neuropathic cough (SNC) can be treated with certain neuralgia medications^1,4,5,6,7,8. What has not yet been described, however, is the use of capsaicin spray as a possible treatment for SNC patients—an approach that may seem counter-intuitive, given that capsaicin is known in the pulmonary medicine literature as a means for provoking coughing for diagnostic or research reasons.

The Genesis of the Idea
In 2005, a desperate patient traveled a considerable distance to consult regarding her terrible intractable cough. She described the typical abrupt, intense tickle at the start of each cough; she also noted the trigger phenomena previously described as a part of SNC². For many years, she had experienced dozens of coughing episodes per day. Many of her episodes lasted a minute or more and, due to the violence of her attacks, led to public humiliation; she suffered from retching, occasional vomiting, and frequent stress incontinence. Based upon this history alone, as well as a negative examination, the criteria for a diagnosis of SNC were met. In addition, she had been previously treated for years for the “usual suspects”—cough-variant asthma, acid reflux, allergy, and post-nasal drip; none of the many medications she had tried for these conditions had helped at all.

Unfortunately, this patient’s case was unusually refractory to our list of SNC medications—in this case, amitriptyline, gabapentin, and oxcarbazepine (later on, she also tried pregabalin). After we managed our customary protocol for each of these medicines by phone across the next few months, we learned together that her cough could be diminished (by as much as 40%), but only if she took high doses of medication, to the point of experiencing unacceptable side effects.

In casting about for additional treatment options, we focused on the fact that her particular stereotyped cough-inducing sensory disturbance was an irresistible tickle at the level of the thyroid cartilage on the left side.

To continue the search for a solution, it seemed logical to infiltrate lidocaine with epinephrine into the area of the left superior laryngeal nerve. Such a nerve block should linger for at least an hour, and since her coughing occurred at least a few times per hour, it seemed that the assessment of benefit, if any, would be easy. After the first injection, the patient reported that she did not cough at all for two days. She was thrilled. Two additional injections were planned in order to validate the benefit of the first injection. Unfortunately, the second injection did not help.

In response to my many questions trying to make sense of the difference between the two injections, the patient commented that the first injection had left her visibly bruised, sore, and somewhat swollen. The second (ineffective) injection did not cause any of these side effects. She in fact requested a third injection that would intentionally make her bruised and sore, as the first one had.

This patient’s story triggered a rapid-fire series of thought experiments: the use of a laser burn as a kind of long-lasting counter-irritant, or the use of extremely powerful mint, or, the use of capsaicin. At that time, capsaicin had been used in topical skin creams to treat various kinds of pain⁹, and also as an intranasal spray for headaches¹⁰.

This patient initially used capsaicin spray obtained for her from a compounding pharmacy, prepared at 0.03% strength. Without any available guidelines, and wanting an answer quickly, I suggested that she use the capsaicin as often as 10 times per day. This gave her heartburn (predictably) and markedly increased her tolerance of hot food. Later, she stepped down to using the capsaicin four times per day. Unfortunately, the capsaicin only helped her cough somewhat. She used it for some time, but then dropped it.

From 2005 to the present, we have tried capsaicin spray in well over a hundred patients. It is typically the fourth approach we try, and only after failure of three different neuralgia medications such as the medications mentioned above, as well as citalopram and desipramine. A small percentage of patients who try capsaicin have experienced major relief. This is why we continue to suggest it as a fourth option.

Possible Kinds of Relief
There appear to be at least three different ways in which capsaicin might relieve an SNC patient’s coughing symptoms. When a patient is supplied his or her first bottle of the spray from us, we explain that we want them to test for the following three potential benefits:

1. May reduce the frequency and severity of coughing attacks. At the outset of our use of capsaicin, our theory was that, if this benefit were to occur, it would be as a counter-irritant, as suggested by the patient anecdote above. Subsequently, we thought that this benefit might occur because of desensitization, via gradual depletion of substance P, a neurotransmitter found in the mucosa¹¹. However, more recent information suggests that capsaicin desensitizes primarily through a process called “defunctionalization” of thermal, mechanical, chemical, and other sensory nerve endings¹². To test capsaicin’s potential to “defunctionalize” nociceptors, we suggest a trial of at least two weeks, using the spray four times per day. The person is told that use of capsaicin can trigger a bout of coughing, much as asthma inhalers that were prescribed by prior physicians often do, and that they must simply carry on with the capsaicin trial for a minimum of two weeks, even in the face of this obnoxious impediment. A number of patients have obtained relief in this way.
2. May act as a counter-irritant to abort or truncate bad attacks. This idea came up because one early patient commented that she was pleased with capsaicin even though her cough frequency was unchanged. She explained that she could tell when an attack was going to be unusually severe and prolonged, often by the “urgency” of the preceding tickle. If she could spray her throat immediately after such an urgent sensation, the attack was shortened. She said that, instead of a typical two-minute duration, the coughing spell might be over in 20 seconds. It is of course impossible to conclude anything from this anecdote, but for what it is worth, other patients have said this works for them, too.
3. May serve as a “cough scheduler” by providing temporary relief from coughing after a capsaicin-induced attack. This idea was contributed by a patient who said that, though capsaicin did not help his coughing problem in either of the two ways mentioned above, he was happy with a different benefit he had discovered:if he used the capsaicin to induce an attack of coughing, he would then enjoy an unusually extended period of time without cough. For example, if he were going to see a play, he would spray his throat just before the play started, have a vigorous attack of coughing as a result, but then be able to get to the intermission without coughing. During the intermission, he would again spray his throat (in the bathroom or outside the theater); a second major episode of coughing would occur, but then he could get through the second half of the performance also without coughing.

How to Apply the Capsaicin
These are the instructions we give our patients for applying the capsaicin spray:

1. Stand in front of your bathroom mirror, open your mouth widely, and try to look as far back into your mouth as possible.
2. Depress your tongue so that, if possible, you see the back wall of your throat, and not just your tongue or palate.
3. Take a deep breath, hold it in, and aim the capsaicin spray straight back, attempting to hit the back wall of the throat, and not the front of the mouth. Immediately after spraying, exhale and swallow. You will feel the “heat” of the capsaicin for at least 5 minutes.
4. Do not eat or drink anything for a minimum of 10 minutes before or after using the spray. This is so that ingested substances do not inadvertently “neutralize” the capsaicin (particularly milk, citrus, salt, etc.).
5. Repeat this routine four times a day for a minimum of two weeks (three is better), before deciding whether or not capsaicin is a worthwhile option.

Going Forward
Our sense is that perhaps no more than one in ten patients who try capsaicin after “failing” the usual neuralgia medications (such as amitriptyline, gabapentin, and several others) end up finding capsaicin to be beneficial, in one or more of the three ways described above. We hope to provide a more formal report of our experience with capsaicin in the near future.

References:

Bastian ZJ, Bastian RW. (2015) The use of neuralgia medications to treat sensory neuropathic cough: our experience in a retrospective cohort of thirty-two patients. PeerJ 3:e816 https://dx.doi.org/10.7717/peerj.816

1. Lee B, Woo P. Chronic cough as a sign of laryngeal sensory neuropathy: diagnosis and treatment. Ann Otol Rhinol Laryngol. 2005; 114: 253-257. ↩

2. Bastian RW, Vaidya AM, Delsupehe KG. Sensory neuropathic cough: a common and treatable cause of chronic cough. Otolaryngol Head and Neck Surg. 2006; 135(1): 17-21. ↩

3. Gibson PG, Ryan NM. Cough pharmacotherapy: Current and future status. Expert Opin Pharmacother. 2011; 12(11): 1745-1755. ↩

4. Halum SL, Sycamore DL, McRae BR. A new treatment option for laryngeal sensory neuropathy. Laryngoscope. 2009; 119:1844-1847. ↩

5. Ryan NM, Birring SS, Gibson PG. Gabapentin for refractory chronic cough: a randomized, double-blind, placebo-controlled trial. Lancet. 2012; 380(9853): 1583-9. ↩

6. Jeyakumar A, Brickman TM, Haben M. Effectiveness of amitriptyline versus cough suppressants in the treatment of chronic cough resulting from postviral vagal neuropathy. Laryngoscope. 2006; 116: 2108-2112. ↩

7. Van de Kerkhove C, Goeminne PC, Van Bleyenbergh P, Dupont LJ. A cohort description and analysis of the effect of gabapentin on idiopathic cough. Cough. 2012; 8(9). ↩

8. Norris BK, Schweinfurth JM. Management of recurrent laryngeal sensory neuropathic symptoms. Ann Otol Rhinol Laryngol. 2010; 119(3): 188-191. ↩

9. Mason L, Moore A, Derry S, Edwards JE, McQuay HJ. Systematic review of topical capsaicin for the treatment of chronic pain. Br Med J. 2004; 328:991–997. ↩

10. Rapoport AM, Bigal ME, Tepper SJ, Sheftell FD. Intranasal medications for the treatment of migraine and cluster headache. CNS Drugs. 2004; 18(10): 671-85. ↩

11. Burks TF, Buck SH, Miller MS. Mechanisms of depletion of substance P by capsaicin. Fed Proc. 1985; 44(9):2531-4. ↩

12. Anand P, Bley K. Topical capsaicin for pain management: therapeutic potential and mechanisms of action of the new high-concentration capsaicin 8% patch. Br J Anaesth. 2011; 107(4):490-502. ↩