AUTHOR=Anand Praveen , Privitera Rosario , Donatien Philippe , Fadavi Hassan , Tesfaye Solomon , Bravis Vassiliki , Misra V. Peter 

TITLE=Reversing painful and non-painful diabetic neuropathy with the capsaicin 8% patch: Clinical evidence for pain relief and restoration of function via nerve fiber regeneration

JOURNAL=Frontiers in Neurology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.998904

DOI=10.3389/fneur.2022.998904

ISSN=1664-2295

ABSTRACT=<sec><title>Introduction</title><p>Current oral treatments for pain in diabetic peripheral neuropathy (DPN) do not affect the progression of DPN i.e., “disease modification.” We assessed whether Capsaicin 8% patch treatment can provide pain relief and also restore nerve density and function <italic>via</italic> nerve regeneration, in both painful (PDPN) and non-painful (NPDPN) diabetic peripheral neuropathy.</p></sec><sec><title>Methods</title><p>50 participants with PDPN were randomized to receive Capsaicin 8% patch Qutenza with Standard of Care (SOC) (PDPN Q+SOC group), or SOC alone (PDPN SOC group). Pain symptoms were assessed with a diary (Numerical Pain Rating Scale, NRPS) and questionnaires. Investigations included quantitative sensory testing (QST) and distal calf skin biopsies, at baseline and 3 months after baseline visit; subsequent options were 3-monthly visits over 1 year. 25 participants with NPDPN had tests at baseline, and 3 months after all received Capsaicin 8% patch treatment.</p></sec><sec><title>Results</title><p>At 3 months after baseline, PDPN Q+SOC group had reduction in NPRS score (<italic>p</italic> = 0.0001), but not PDPN SOC group. Short-Form McGill Pain Questionnaire (SF-MPQ) showed significant reductions in scores for overall and other pain descriptors only in the PDPN Q+SOC group. Warm perception thresholds were significantly improved only in the PDPN Q+SOC group (<italic>p</italic> = 0.02), and correlated with reduction in SF-MPQ overall pain score (<italic>p</italic> = 0.04). NPDPN Q+SOC group did not report pain during the entire study. Density of intra-epidermal nerve fibers (IENF) with PGP9.5 was increased at 3 months in PDPN Q+SOC (<italic>p</italic> = 0.0002) and NPDPN Q+SOC (<italic>p</italic> = 0.002) groups, but not in the PDPN SOC group. Increased sub-epidermal nerve fibers (SENF) were observed with GAP43 (marker of regenerating nerve fibers) only in PDPN Q+SOC (<italic>p</italic> = 0.003) and NPDPN Q+SOC (<italic>p</italic> = 0.0005) groups. Pain relief in the PDPN Q+SOC group was correlated with the increased PGP9.5 IENF (<italic>p</italic> = 0.0008) and GAP43 (<italic>p</italic> = 0.004), whereas those with lack of pain relief showed no such increase; in some subjects pain relief and increased nerve fibers persisted over months. PGP9.5 IENF increase correlated with axon-reflex vasodilatation in a NPDPN Q+SOC subset (<italic>p</italic> = 0.006).</p></sec><sec><title>Conclusions</title><p>Capsaicin 8% patch can provide pain relief <italic>via</italic> nerve regeneration and restoration of function in DPN (disease modification). It may thereby potentially prevent diabetic foot complications, including ulcers.</p></sec>