Publications

Topical Innovations is founded in 2016, and its Intellectual Property Platform consists of 2 patents, based on insights in the development of topical analgesic creams gathered during more than a decade. From 2010 onwards a steady stream of publications on the efficacy and benefits of topical creams followed.

References

• • Keppel Hesselink JM, Kopsky DJ, Bhaskar AK. Ethical justification of single-blind and doubleblind placebo-controlled response tests in neuropathic pain and N-of-1 treatment paradigm in clinical settings. J. Pain Res. 2019; 12: 345–352. (PDF)
  • Keppel Hesselink JM, Kopsky DJ. Neuropathic pain due to chronic idiopathic axonal neuropathy: fast pain reduction after topical phenytoin cream application. Open J Pain Med. 2018; 2(1): 007-008. (PDF)
  • Kopsky DJ, Keppel Hesselink JM. Opioid Receptors in the Skin. Austin J Anesthesia and Analgesia. 2018; 6(2): 1074. (PDF)
  • Kopsky DJ, Keppel Hesselink JM. Identification of responders for pain treatments: did we find the holy grail? Neurological Disorders & Epilepsy Journal. 2018; 1(2):117. (PDF)
  • Kopsky DJ, Keppel Hesselink JM. Single-blind placebo-controlled response test with phenytoin 10% cream in neuropathic pain patients. Pharmaceuticals 2018; 11: 122. (PDF)
  • Keppel Hesselink JM, Kopsky DJ. On the importance of precision medicine for neuropathic pain. Pharm Pharmacol Int J. 2018;6(6):432-433. (PDF)
  • Keppel Hesselink JM, Kopsky DJ. [Topical compounded analgesics for neuropathic pijn] Topicale magistrale analgetica voor neuropathische pijn. Nederlandstalig Tijdschrift Pijnbestrijding. 2018; 37(73): 6-9. (PDF)
  • Keppel Hesselink JM. Pain in chemotherapy-induced peripheral neuropathy: NGF and the logic of topical phenytoin cream. J Case Rep Clin Images. 2018; 2: 1008. (PDF)
  • Bartollino S, Chiosi F, di Staso S,Uva M, Pascotto A,Rinaldi M, Keppel Hesselink JM, Costagliola C. The retinoprotective role of phenytoin. Drug Des Devel Ther. 2018;12: 3343-3356. (PDF)
  • Keppel Hesselink JM. Chronobiology of neuropathic pain and the use of topical phenytoin in painful diabetic neuropathy. J Diabetol 2018; 2(2): 3-5. (PDF)
  • Keppel Hesselink JM. Phenytoin cream in painful diabetic neuropathy: an evolving chapter. J Diabetol 2018; 2(2): 6-8. (PDF)
  • Keppel Hesselink JM. A case of wasp-induced pain treated with topical phenytoin cream. J Clin Cases Rep  2018; 1(3): 106-108. (PDF)
  • Keppel Hesselink JM. The quest for better analgesics for the treatment of peripheral neuropathic pain: navigating the sodium channels. Trends Gen Pract. 2018; 1(2): 2-3. (PDF)
  • Kopsky DJ, Keppel Hesselink JM. A single-blind n-of-1 study evaluating 4 different doses of phenytoin in a topical analgesic cream for the treatment of peripheral neuropathic pain. J Pain Manage Ther. 2018;2(1):17-20. (PDF)
  • Keppel Hesselink JM, Kopsky DJ. Repositioning problems of clonidine as topical formulation in neuropathic pain. EC Pharmacology and Toxicology 2018; 6(8): 756-762. (PDF).
  • Keppel Hesselink JM, Kopsky DJ. Fast onset of relief after topical phenytoin in neuropathic pain after chemotherapy. Trends Cancer Res Chemother. 2018;1(1):1-3. (PDF)
  • Keppel Hesselink JM, Kopsky DJ. Topical analgesics in localized neuropathic pain: transdermal delivery or intradermal? Anaesthesia, Critical Care and Pain Management. 2018; 1(2): 86-89. (PDF)
  • Keppel Hesselink JM. Posttranslational sodium ion channel modifications and the use of topical phenytoin in Painful Diabetic Neuropathy (PDN). Int J Diabetes Metab Disord 2018; 3(1)1-3. (PDF)
  • Keppel Hesselink JM, Notermans NC. Topical phenytoin formulations for pain in small fiber neuropathy, a pathogenetic approach. Gen Int Med Clin Innov. 2018; 3(1): 2-4. (PDF)
  • Kopsky DJ, Keppel Hesselink JM. Phenytoin Cream for the Treatment of Neuropathic Pain: Case Series. Pharmaceuticals (Basel). 2018;11(2): E53. (PDF)
  • Keppel Hesselink JM. How to Define Neuroprotection: The Case of Phenytoin. Open Access J Neurol Neurosurg. 2018; 7(4): 555719. (PDF)
  • Keppel Hesselink JM. Topical NaV1.7 channel blocker failed in postherpetic Neuralgia (PHN): lessons to learn. Gen Med Open. 2018; 2(2): 1-2. (PDF)
  • Keppel Hesselink JM, Kopsky DJ. The individualized N-of-1 trial: dose-response in a single-blind cross-over response test of phenytoin 10% and 30% cream in neuropathic pain. EC Anaesthesia 2018; 4(6):1-6. (PDF)
  • Keppel Hesselink JM, Mulder JK, Kopsky DJ. Rationale for the repositioning of phenytoin as a topical analgesic for peripheral neuropathic pain and a personalized and investigator-driven development plan. Ann Pharmacol Pharm. 2018; 3(2): 1144. (PDF)
  • Keppel Hesselink JM. Single-blind placebo-controlled response on phenytoin 10% in painful diabetic neuropathy. Gen Med Open. 2018; 2(1): 2-3. (PDF)
  • Kopsky DJ, Keppel Hesselink JM. Phenytoin in topical formulations augments pain reduction of other analgesics in the treatment of neuropathic pain. Int J Anesthetic Anesthesiol 2018; 5: 061. (PDF)
  • Keppel Hesselink JM. Topical phenytoin in painful diabetic neuropathy: rationale to select a non-selective sodium channel blocker. Clinical research in Neurology. 2018; 1(1): 1-5.
  • Keppel Hesselink JM. Phenytoin cream in painful diabetic neuropathy: support for development of new indications for generic drugs needed. Austin Neurology 2018; 3(1): 1011.
  • Keppel Hesselink JM, Kopsky DJ. The value of placebos to individualize pain therapy via a new single-blind test paradigm identifying responders on topical analgesic interventions. J Pain Relief  2018; 7: 313. (PDF)
  • Keppel Hesselink JM. Phenytoin: repurposing an old molecule and patent strategies for neuropathic pain. J Clin Trials Pat 2018;3(1): 3. (PDF)
  • Keppel Hesselink JM, Kopsky DJ. Small fiber burning pain in diabetic neuropathy in the elderly, treated with phenytoin cream. BAOJ Anesthesia 2018; 2(1): 003. (PDF)
  • Keppel Hesselink JM. A rationale for using gabapentinoids in topical analgesic formulations? Anaesthesia, Critical Care and Pain Management 2018; 1(3): 59-62. (PDF)
  • Keppel Hesselink JM, Kopsky DJ. The use of topical compounded analgesic creams in neuropathic pain by the primary care physician. J Gen Pract (Los Angel) 2017; 5:345. (PDF)
  • Keppel Hesselink JM. Analgesic onset of action or onset of relief in neuropathic pain. Anaesthesia, Critical Care and Pain Management 2017; 1(2): 48-50. (PDF)
  • Keppel Hesselink JM. Topical amitriptyline: can it reduce localized neuropathic pain? J Clin Trials Regul Aff. 2017; 1(1): 1-4. (PDF)
  • Keppel Hesselink JM, Kopsky DJ. Topical compounded analgesic treatment in neuropathic pain: 8 years of experience. J Pain Manage Med. 2017;3(2): 128. (PDF)
  • Keppel Hesselink JM. Rethinking peripheral sensitization, peripheral neuropathic pain and the putative value of topical analgesics. J of Pharmacol & Clin Res. 2017; 4(2): 555631. (PDF)
  • Keppel Hesselink JM. Repurposing phenytoin as an anti-aggression drug: clinical evidence. Neurol Disord Therap 2017; 1(4)1-5. (PDF)
  • Keppel Hesselink JM, Kopsky DJ. Topical phenytoin cream in small fiber neuropathic pain: fast onset of perceptible pain relief. Int J Pain Relief. 2017;1(1): 015-019. (PDF)
  • Keppel Hesselink JM, Kopsky DJ. Topical analgesia: transdermal or ‘intradermal’ mechanisms of action? Sci J Neurol Neurosurg. 2017;3(3): 066-069. (PDF)
  • Keppel Hesselink JM, Kopsky DJ. Phenytoin cream reduces pain and improves sleep in patients suffering from neuropathic pain. Austin J Anesthesia and Analgesia. 2017; 5(2): 1061. (PDF)
  • Keppel Hesselink JM, Kopsky DJ. Pain in chemotherapy induced peripheral neuropathy treated with topical phenytoin cream. CP Cancer Sci. 2017 1(2): 008. (PDF)
  • Keppel Hesselink JM, Schatman ME. Phenytoin and carbamazepine in trigeminal neuralgia: marketing-based versus evidence-based treatment. J. Pain Res. 2017; 10: 1663-1666. (PDF)
  • Keppel Hesselink JM. Phenytoin repositioned in wound healing: clinical experience spanning 60 years. Drug Discov Today. 2017 Oct 6.
  • Chiosi F, Keppel Hesselink JM, Rinaldi M, Di Staso S, Bartollino S, Costagliola C. Phenytoin: its potential as neuroprotective and retinoprotective drug. Br J Clin Pharmacol. 2017 Oct 12.
  • Keppel Hesselink JM. Phenytoin: a step by step insight into its multiple mechanisms of action-80 years of mechanistic studies in neuropharmacology. J Neurol. 2017; 264(9), 2043-2047.
  • Keppel Hesselink JM, Kopsky DJ. Phenytoin: neuroprotection or neurotoxicity? Neurol Sci. 2017 Jun;38(6):1137-1141.
  • Keppel Hesselink JM, Kopsky DJ. Topical phenytoin cream reduces burning pain due to small fiber neuropathy in sarcoidosis. J Anesth Pain Med. 2017; 2(1): 1-3. (PDF)

• • Keppel Hesselink JM. Amantadine and phenytoin: patent protected cases of drug repositioning Clin Invest. 2017; 7(1):11-16.

• • Keppel Hesselink JM, Kopsky DJ, Stahl SM. Bottlenecks in the development of topical analgesics: molecule, formulation, dose finding, and phase III design. J Pain Res. 2017; 10: 635-641. (PDF)

• • Keppel Hesselink JM, Kopsky DJ. Burning pain in small fibre neuropathy treated with topical phenytoin: rationale and case presentations. J Clin Anesth Pain Med. 2017; 1(1): 6. (PDF)

• • Kopsky DJ, Keppel Hesselink JM. Phenytoin in topical formulations augments pain reduction of other topically applied analgesics in the treatment of trigeminal neuralgia. J. Clin Anesth.  2017; 38: 154-155.

• • Keppel Hesselink JM, Kopsky DJ. Topical phenytoin in neuralgic pain, peripheral modulation of central sensitization: two case reports. J Pain Relief  2017; 6(2): 284. (PDF)

• • Kopsky DJ, Keppel Hesselink JM. Topical phenytoin for the treatment of neuropathic pain. J Pain Res. 2017; 10:469-473. (PDF)

• • Keppel Hesselink JM, Kopsky DJ. Phenytoin: 80 years young, from epilepsy to breast cancer, a remarkable molecule with multiple modes of action. Journal of Neurology. 2017:1-5.

• • Keppel Hesselink JM, Kopsky DJ, AK Bhaskar. Skin matters! The role of keratinocytes in nociception: a rational argument for the development of topical analgesics. J Pain Res. 2017; 10:1-8. (PDF).

• • Keppel Hesselink JM.  Thinking out of the pillbox: the relevance to topiceuticals in the treatment of neuropathic pain. J Pain Relief 2016; 6(5): (PDF).

• • Keppel Hesselink JM, Kopsky DJ, Sajben NL. New topical treatment of vulvodynia based on the pathogenetic role of cross-talk between nociceptors, immunocompetent cells and epithelial cells. J Pain Res. 2016; 9: 757-762. (PDF)

• • Keppel Hesselink JM, Kopsky DJ. Topical analgesic creams and nociception in diabetic neuropathy: towards a rationale fundament. Clin Case Rep Rev. 2016; 2(7): 500-502. (PDF)
  • Keppel Hesselink JM. Topical analgesics: critical issues related to formulation and concentration. J Pain Relief 2016; 5(6):245. (PDF)

• • Kopsky DJ. Topical analgesia is a viable option. J Pain Relief 2016; 5(3):245. (PDF)

• • Kopsky DJ. Extending the therapeutic scope for the treatment of neuropathic pain with topical analgesics. J Pain Relief. 2016; 5(3): 251-252. (PDF)

• • Kopsky DJ, Keppel Hesselink JM, Bhaskar AK, Hariton G, Romanenko V, Casale R. Analgesic effects of topical ketamine. Minerva Anestesiol. 2015;81(4):440-449.

• • Kopsky DJ, Keppel Hesselink JM, Casale R. Walking with Neuropathic Pain: Paradoxical Shift from Burden to Support? Case Rep Med. 2015;2015:764950. (PDF)

• • Keppel Hesselink JM, Kopsky DJ, Sajben NL. Vulvodynia and proctodynia treated with topical baclofen 5 % and palmitoylethanolamide. Arch Gynecol Obstet. 2014 Aug;290(2):389-93.

• • Keppel Hesselink JM, Kopsky DJ. Treatment of chronic regional pain syndrome type 1 with palmitoylethanolamide and topical ketamine cream: modulation of nonneuronal cells. J Pain Res. 2013 Mar 21;6:239-45. (PDF)

• • Kopsky DJ, Keppel Hesselink JM. Neuropathic pain as a result of acromegaly, treated with topical baclofen cream.J Pain Symptom Manage 2013 Oct;46(4):e4-5.

• • Kopsky DJ, Liebregts R, Keppel Hesselink JM. Central neuropathic pain in a patient with multiple sclerosis treated successfully with topical amitriptyline.Case Rep Med. 2012;2012:471835. (PDF)

• • Kopsky DJ, Amelink GJ, Keppel Hesselink JM. Intractable neuropathic pain in spinal intramedullary cavernoma treated successfully with a novel combination cream. Pain Med. 2012 May;13(5):729-30. (PDF)

• • Keppel Hesselink JM, Kopsky DJ. Intractable neuropathic pain due to ulnar nerve entrapment treated with cannabis and ketamine 10%. J Clin Anesth. 2012 Feb;24(1):78-9.

• • Kopsky DJ, Keppel Hesselink JM. Multimodal Stepped Care Approach Involving Topical Analgesics for Severe Intractable Neuropathic Pain in CRPS Type 1: A Case Report. Case Rep Med. 2011;2011:319750. (PDF)

• • Kopsky DJ, Keppel Hesselink JM. High doses of topical amitriptyline in neuropathic pain: two cases and literature review. Pain Pract. 2012 Feb;12(2):148-53. (PDF preview)

• • Liebregts R, Kopsky DJ, Keppel Hesselink JM. Topical amitriptyline in post-traumatic neuropathic pain.J Pain Symptom Manage. 2011 Apr;41(4):e6-7.

• • Keppel Hesselink JM, Kopsky DJ. Letter to the editor. Curr Ther Res Clin Exp. 2010 Dec;71(6):416-7. (PDF)

• Kopsky DJ, Keppel Hesselink JM. A new combination cream for the treatment of severe neuropathic pain. J Pain Symptom Manage. 2010 Feb;39(2):e9-e10. (PDF)