Category Archives: Deafferentation Pain

Smearing Pain Away with Ambroxol 20% Cream

Feature Image of Ambroxol molecule sourced from:

https://en.wikipedia.org/wiki/Ambroxol

Dear Pain Matters readers,

Treatment via topical* Ambroxol* 20% cream may offer significant pain relief from severe and localised nerve pain conditions including:

  • Complex regional pain syndrome (CRPS);
  • Trigeminal nerve pain;
  • Postherpetic nerve pain;
  • Phantom limb pain;
  • Deafferentation pain;
  • Post-surgical nerve pain;
  • Nerve pain in both feet; and
  • Multifocal neuropathy.

Prepared by a local pharmacist, topical Ambroxol 20% cream comprises:

  • Ambroxol;
  • Dimethyl sulfoxide; and
  • Linola cream (that includes linoleic acid).

Specifically, 50.0 g of topical Ambroxol 20% cream contains Ambroxol (10.0 g), dimethyl sulfoxide (5.0 g) and Linola cream (up to 50.0 g for the total mixture) (Kern & Weiser, 2015).

220px-Ambroxol_ball-and-stick.png

Ball-and-stick model of Ambroxol molecule sourced from:

https://en.wikipedia.org/wiki/Ambroxol

As a strong local anaesthetic, Ambroxol works by blocking sodium channels, and in particular, the TTX-resistant (TTX-r) Nav1.8 sodium channel.  In fact, Ambroxol is 40 times more potent than lidocaine.  Preferentially expressed in nociceptive C-fibres, Nav1.8 may be upregulated during inflammation and pain (Weiser, 2006).

Topical Ambroxol for Complex Regional Pain Syndrome 

Eight (8) patients who suffered from CRPS for less than a year received topical Ambroxol 20% cream, together with standard treatments.

Topical Ambroxol resulted in many therapeutic benefits including:

  • Less spontaneous pain and pain during movement (N=6);
  • Less allodynia and hyperalgesia (N=6 and N=7, respectively);
  • Decreased swelling and skin reddening (N=7 and N=4, respectively) as well as enhanced skin temperature (N=4); and
  • Improved motor dysfunction (N=6).

In summary, topical Ambroxol 20% cream may be a useful treatment option for CRPS (Maihöfner et al, 2018).

Topical Ambroxol for Trigeminal Nerve Pain 

Five (5) patients with trigeminal neuralgia suffered pain attacks while 3 of them also endured spontaneous pain.  Their facial pain levels ranged from 4 to 10 (out of 10, using the Numerical Rating Scale; NRS).

The good news:

All 5 patients enjoyed significant pain reductions including decreased pain attacks following application of topical Ambroxol 20% cream (in addition to standard treatment).  Specifically, their pain levels dropped between 2 to 8 points (out of 10, using NRS) within only 15 to 30 minutes following topical Ambroxol treatment.   Pain relief lasted 4 to 6 hours.

Pain was completely eliminated in one patient after a week of topical Ambroxol treatment, while 2 patients were able to reduce their medication intake.

There were no adverse effects nor skin reactions.

In summary, topical Ambroxol 20% cream can lead to significant pain relief from trigeminal neuralgia within 15 to 30 minutes following application thereof onto painful areas (Kern et al (2019).

Topical Ambroxol for Severe Chronic Pain – 7 Successful Cases

Overview

A German study reviewed the effects of topical Ambroxol on 7 patients (2 females; 5 males) with severe nerve pain.

Specifically, 2 patients had postherpetic nerve pain while the remaining 5 suffered from phantom limb pain, deafferentation pain, post-surgical nerve pain, nerve pain in both feet and multifocal neuropathy.  Their average pain levels ranged from 4 to 6, while their maximum pain reached 6 to 10 (NRS).

Four (4) patients had tried lidocaine 5% without success, while a 5th patient did not benefit from capsaicin 8%.

The good news:

All 7 pain patients enjoyed pain relief within 5 to 30 minutes after topical application of Ambroxol 20% cream onto painful areas (details follow).  The topical Ambroxol-evoked pain relief included reduced pain attacks and lasted 3 to 8 hours.  Four (4) patients had improved mobility, better sleep and other benefits.

There were no adverse effects nor skin changes during application of topical Ambroxol, even 4 years later.

Case 1 – Local Nerve Pain in Both Feet

A male patient named John** (born in 1942) suffered from nerve pain in both forefeet despite topical lidocaine 5 % plasters and other pain treatments.

The goods news:

John first started using topical Ambroxol in June 2011.  Within 5 minutes, the stabbing pain and allodynia (8/10) in both of his feet disappeared completely for more than 8 hours.  Furthermore, John was able to significantly reduce his Gabapentin intake and discontinue opiates altogether.

At follow-up after 4 years, John continued to be successfully treated with topical Ambroxol.  As a result, John was able to enjoy walking and gardening again.

Case 2 – A Double Amputee with Cold Phantom Limb Pain

Both of Joe’s** lower legs were amputated due to peripheral arterial occlusive disease and diabetes mellitus.

Joe regularly suffered severe cold phantom limb pain (7–9, out of 10) that shifted from his missing toes to the balls of his phantom feet.  These spontaneous bursts of pain usually lasted anywhere from a few minutes to many hours and even affected his sleep.

Joe’s pain treatment including opiates and anticonvulsants failed to offer pain relief.

One day, 15 minutes after applying topical Ambroxol 20% cream onto his stumps, Joe finally found significant relief from his cold phantom limb pain.  This pain relief that also included warmer phantom limbs lasted several hours.

At the 11-month follow-up, Joe continued to enjoy pain relief without skin changes nor other side effects thanks to regular application of topical Ambroxol 20% cream onto his stumps.

Case 3 – Chronic Knee Pain Following Total Knee Replacement 

After a total knee replacement in November 2010, Jan** (58) suffered ongoing nerve pain including allodynia and hyperalgesia in her knee.

Despite pain treatments including Tapentadol (that replaced Buprenorphine), lidocaine patches and capsaicin 8 % plasters, Jan was unable to find pain relief.

One day, within only 15 minutes following application of topical ambroxol 20% cream to her painful knee, Jan finally found (quoting) ‘clear pain relief’!  The burning and stabbing in her knee was significantly reduced while the ‘raging feeling’ in her knee was almost gone.

At follow-up almost one year later, Jan continued to enjoy substantial pain relief for 4 – 6 hours following repeated application of the topical ambroxol 20% cream.  Specifically, her average knee pain levels dropped from 8 down to 4 (and sometimes even lower, down to 1).  There were no skin changes nor other side effects.

Case 4 – Deafferentation Pain after a Motorbike Accident

A patient (38) named Allan** suffered deafferentation pain in his  left arm including allodynia in his hand and forearm due to a plexus lesion caused by a motorcycle accident in 1997.

Despite a nerve graft, ketamine, gabapentin, a lidocaine infusion and lidocaine plasters as well as mirror therapy, Allan’s pain was severe and relentless.

The sedative effects of amitriptyline treatment were intolerable, as were the psychoactive effects of cannabis.

Trigger point treatment and Tapentadol were also not tolerated.

Despite being on pregabalin and duloxetine, Allan suffered ‘burning pain’, ‘crushing underlying pain’ and ‘shooting tingling pains’, with pain levels ranging from 4 to 8 (of 10).

One day, topical Ambroxol 20% cream was applied over Allan’s pectoral muscle.

Guess what happened next?

The shooting and tingling pains dropped from 8/10 to 4/10!

Substantial pain relief would kick in within 15 minutes and last for 4 to 6 hours following regular application of topical Ambroxol 20% cream.  Allan’s sleep improved and his spasms and cramps disappeared.

Unfortunately, the ‘deep underlying pain’ persisted despite topical Ambroxol 20% cream treatment (and pregabalin and duloxetine).

Case 5 – Postherpetic Nerve Pain on Chest

A male patient named Pete** (55) suffered postherpetic nerve pain (5/10) and allodynia on the right side of his chest.

Whilst lidocaine plasters helped relieve his pain, the plasters could not cover all the painful skin regions.

One day, Pete added topical Ambroxol 20% cream to his pain management protocol.  Analgesia occurred in only 30 minutes after topical application of Ambroxol cream to areas not covered by lidocaine patches.  Pain attacks reduced from 6/10 to 4/10 and this pain relief was sustained for 4 to 6 hours. There were no skin reactions nor other side effects, even after 3 years of Ambroxol cream treatment.

Case 6 – Multifocal Neuropathy

A male patient named Sam** suffered nerve pain in the arch of his left foot as well as multifocal neuropathy*** caused by vasculitis.  Sam’s persistent pain including severe pain attacks (8/10, especially in the evenings and at night) prevented him from engaging in activities.

Although amitriptyline drops helped with sleep, lidocaine patches, peripheral analgesics and Tilidine did not offer pain relief.

In December 2013, Sam tried topical Ambroxol cream for the first time.

The good news:

Within only 15 minutes of topical Ambroxol application in the evening, Sam’s nerve pain levels were significantly reduced from 6/10 to 2/10.  This pain relief lasted more than 6 hours, hence improving his sleep.  Sam was also able to stop using Zolpidem.

After 4 months of topical Ambroxol cream treatment, Sam’s underlying pain during the daytime had almost vanished.

At the 17-month follow-up, Sam continued to obtain pain relief from topical Ambroxol treatment without any skin reactions nor other side effects.

Case 7 – Trigeminal Postherpetic Nerve Pain

A 91-year old female patient named Edith** suffered facial nerve pain up to 8/10 and poor sleep after a zoster infection of the maxillary branch of the left trigeminal nerve in June 2014.

While lidocaine patches offered pain relief, there were bad skin reactions.

Edith finally enjoyed pain relief and better sleep after starting topical Ambroxol 20% cream.

Repeated application led to consistent pain relief including a ‘calmer’ cheek within only 15 minutes, as confirmed at the 11-month follow-up.

There were no adverse effects.

Mechanisms

The Nav1.8 sodium channel plays a key role in certain pain mechanisms while TTX-sensitive sodium channels contribute to others.  Sodium channels including TTX-r Nav1.8 are upregulated during inflammation in many pain conditions (e.g. trigeminal neuralgia).

As a strong sodium channel blocker, Ambroxol preferentially blocks TTX-r Nav1.8.  Specifically, a study confirmed that Ambroxol blocked resting TTX-r sodium channels more potently than lidocaine, mexiletine or benzocaine.  Thus, Nav1.8-mediated nerve pain may be blocked by topical Ambroxol (Weiser, 2006).  Similar results were reported by other studies (Gaida et al, 2005; Hama et al, 2010; Moon et al, 2012).

Another local anesthetic called Mepivacaine also blocks Nav1.8, contrary to Bupivacaine that inhibits TTX-sensitive sodium channels instead (Leffler et al, 2010).

Warning: Possible Adverse Effects of Ambroxol

Like most drugs, Ambroxol can cause serious side effects (Kreicas, 2016; Combalia et al, 2017).

Studies reported that adverse effects usually arose after systemic intake (e.g. oral ingestion), as opposed to topical application, of Ambroxol (Monzón et al, 2009).

Summary

Ambroxol is a strong local anaesthetic and peripheral analgesic that selectively targets and potently blocks the TTX-r Nav1.8 that may play a role in many nerve pain conditions.

As such patients with localised nerve pain may obtain significant pain relief from topical Ambroxol cream that preferentially targets TTX-r Nav1.8.

Topical Ambroxol is non-addictive and relatively safe for long-term use (subject to medical supervision) (Kern & Weiser, 2015; Kern & Weiser, 2015 (Poster 239)****; Casale et al, 2017).

Now that’s a good way to cover up localised nerve pain!

Sabina Walker

Blogger, Pain Matters (in WordPress)

KEY

* Topical means locally through the skin.

* Ambroxol is sometimes called na872.

** Not his/her real name.

*** Multifocal neuropathy is sometimes called mononeuritis multiplex or mononeuropathy multiplex.

**** Poster 239 by Kern & Weiser (2015) outlines several more successful cases not mentioned above.  See Poster 239 for further details.

REFERENCES

Clinical Papers

Topical Ambroxol for Complex Regional Pain Syndrome 

(1A) Maihöfner et alSuccessful treatment of complex regional pain syndrome with topical ambroxol: a case series. Pain Management (

https://doi.org/10.2217/pmt-2018-0048

Topical Ambroxol for Trigeminal Nerve Pain  

(1B) Kern et al. Topical Ambroxol 20% for the Treatment of Classical Trigeminal Neuralgia – A New Option? Initial Clinical Case Observations. Headache The Journal of Head and Face Pain (17 January 2019);

https://www.researchgate.net/publication/330524533_Topical_Ambroxol_20_for_the_Treatment_of_Classical_Trigeminal_Neuralgia_-_A_New_Option_Initial_Clinical_Case_Observations

Topical Ambroxol for Severe Chronic Pain – 7 Successful Cases

(1C) Kern & Weiser. Topical ambroxol for the treatment of neuropathic pain. An initial clinical observation. [in German: Topisches Ambroxol zur Behandlung neuropathischer Schmerzen.] Schmerz (20 November 2015); 29 Suppl 3: S89-96.

doi: 10.1007/s00482-015-0060-y

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4701773/

(1D) Kern and Weiser. Topical Ambroxol for the treatment of neuropathic or severe nociceptive pain – First case reports. 9th Congress of the European Pain Federation (EFIC) (Sept 2015: Vienna); Poster 239.

doi: 10.13140/RG.2.2.35671.27041

https://www.researchgate.net/publication/308720424_Topical_Ambroxol_for_the_treatment_of_neuropathic_or_severe_nociceptive_pain_-_First_case_reports

Related Papers and Articles

(1E) Casale et al. Topical Treatments for Localized Neuropathic Pain. Curr Pain Headache Rep (2017); 21(3): 15.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5340828/

Mechanisms

(2A) Weiser, T. Comparison of the effects of four Na+ channel analgesics on TTX-resistant Na+ currents in rat sensory neurons and recombinant Nav1.2 channels.  (13 March 2006); 395(3):179-84.

https://www.ncbi.nlm.nih.gov/pubmed/16293367

(2B) Gaida et al. Ambroxol, a Nav 1.8-preferring Na(+) channel blocker, effectively suppresses pain symptoms in animal models of chronic, neuropathic and inflammatory pain. Neuropharmacology (2005); 49: 1220–1227.

doi: 10.1016/j.neuropharm.2005.08.004.

https://www.ncbi.nlm.nih.gov/pubmed/16182323

(2C) Hama et al. Antinociceptive effect of ambroxol in rats with neuropathic spinal cord injury pain. Pharmacol Biochem Behav (2010); 97: 249–255.

doi: 10.1016/j.pbb.2010.08.006

https://www.ncbi.nlm.nih.gov/pubmed/20732348

(2D) Leffler et al. Block of sensory neuronal Na+ channels by the secreolytic ambroxol is associated with an interaction with local anesthetic binding sites. Eur J Pharmacol (2010)630:19–28.

doi: 10.1016/j.ejphar.2009.12.027

https://www.ncbi.nlm.nih.gov/pubmed/20044988

(2E) Moon et al. The differential effect of intrathecal Nav1.8 blockers on the induction and maintenance of capsaicin- and peripheral ischemia-induced mechanical allodynia and thermal hyperalgesia.  (Jan 2012); 114(1): 215-23.

doi: 10.1213/ANE.0b013e318238002e.

https://www.ncbi.nlm.nih.gov/pubmed/22127815

(2F) Weiser, Thomas. Ambroxol: a CNS drug?. CNS Neurosci Ther (2008); 14(1): 17-24.

doi 10.1111/j.1527-3458.2007.00032.x.

https://www.researchgate.net/publication/5369710_Ambroxol_a_CNS_drug

(2G) Weiser, Thomas. Nav1.8 channel blockade as an approach to the treatment of neuropathic pain. Drugs of the Future (July 2006); 31(7); 597.

10.1358/dof.2006.031.07.1005296.

https://www.researchgate.net/publication/274516492_Nav18_channel_blockade_as_an_approach_to_the_treatment_of_neuropathic_pain

Warning: Possible Adverse Effects of Ambroxol

(3A) Kreicas, Leonard. Topical ambroxol possible treatment of neuropathic pain. Nerve Neuropathy (1/6/2016).

http://nerveneuropathy.com/topical-ambroxol-possible-treatment-of-neuropathic-pain/

(3B) Combalia et al. Stevens–Johnson syndrome probably induced by ambroxol. CED (24 April 2017); 42(4): 465-467.

doi.org/10.1111/ced.13094

https://onlinelibrary.wiley.com/doi/full/10.1111/ced.13094

(3C) Monzón et al (2009). Ambroxol-induced systemic contact dermatitis confirmed by positive patch test. Allergologia et immunopathologia (2009); 37: 167-8.

doi: 10.1016/S0301-0546(09)71730-6

https://www.researchgate.net/publication/26827245_Ambroxol-induced_systemic_contact_dermatitis_confirmed_by_positive_patch_test

(3D) Benstetter, Monika. Ambroxol and bromhexine expectorants: safety information to be updated. European Medicines Agency (27/02/2015).

https://www.ema.europa.eu/en/news/ambroxol-bromhexine-expectorants-safety-information-be-updated

 

 

 

 

 

Advertisements