Neuropathic pain is associated with a functional abnormality of the nervous system due to a direct lesion or disease of the somatosensory system. In this framework, capsaicin has been used in several clinical settings as a topical medication to treat neuropathic pain. We report three cases of persistent neuropathic pain who underwent this protocol: three applications of the capsaicin 8% patch separated by one month.

Background. Capsaicin has been used in several clinical settings as a topical medication to treat pain derived from different conditions. It selectively stimulates nociceptive neurons and has been widely used to study pain-related events. It has been demonstrated that capsaicin activates TRPV1 (the trnsient receptor potential vanilloid subtype 1) [1]. TRPV1 is mainly expressed in neuronal cells, as trigeminal nerves, and dorsal region ganglia [2]. Capsaicin has a selective action on C-polymodal nociceptors, also mediated by reactive oxygen species (ROS). High or repeated doses of capsaicin induce an initial pain sensation, followed by analgesia. After exposure to a high or repeated dose of capsaicin, the TRPV1 receptors begin a refractory state commonly termed as desensitization which leads to inhibition of receptor function [2]. Some studies indicated capsaicin participation in neurotransmission in a TRPV1-independent manner. It seems to be able to modulate the synaptic transmission acting through pre- and postsynaptic mechanisms [3]

Cases report. CASE 1, POST HERPETIC NEURALGIA (PHN) (Figure 1, 2): 41 years-old male patient affected by persistent pain lasting for 1 year, due to post herpetic neuralgia involving the area covered by the supraorbital nerve. At the cellular level, PHN upregulates the receptors typically associated with pain, such as TRPV1 [4]. After the tratment the outcome has resulted to a significant reduction of the symptoms : the pain relief has maintained, staggered only by sporadic episodes of itching. CASE 2 DEAFFERENTATION (Figure 3, 4): A 32 years-old male patient has had post-inguinal herniorrhaphy   painful consequences due to triple neurotomy for 48 months. The clinical outcome at the end of the therapy consists  of a reduction of 50% of the initial pain. CASE 3, CRPS I (complex regional pain syndrome) (Figure 5, 6): A 20-years old female patient presenting persistent pain in the left ankle in CPRS-I consequent to a distorsive trauma. The woman underwent the implantation of a perinervous neurostimulator on sural nerve, with acceptable control of the pain, but without relief from the vasomotor manifestation and the persistence of cutaneous hyperalgesia. After the treatment with Capsaicin patch After an initial stage of worsening of symptoms, we have detected a reduction of the intensity of the pain.

Conclusions: The treatment is effective in reducing the intensity of resistant pain, and it consists of a valid therapy for the treatment of the chronic neuropathic pain administered in association with other drugs.

Declarations. Written informed consent was obtained from all patient. All methods were carried out in accordance with relevant guidelines and regulations of ethical principles for medical research involving human, stated in the Declaration of Helsinki.