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
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Author(s)
Type
Journal Article
Abstract
Introduction: 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 via nerve regeneration, in both painful (PDPN) and non-painful (NPDPN) diabetic peripheral neuropathy.
Methods: 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.
Results: At 3 months after baseline, PDPN Q+SOC group had reduction in NPRS score (p=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 (p=0.02), and
correlated with reduction in SF-MPQ overall pain score (p=0.04). NPDPN Q+SOC group did not report pain during the entire study.
Density of intra-epidermal nerve fibres (IENF) with PGP9.5 was increased at 3 months in PDPN Q+SOC (p=0.0002) and NPDPN Q+SOC
(p=0.002) groups, but not in the PDPN SOC group. Increased sub-epidermal nerve fibres (SENF) were observed with GAP43 (marker
of regenerating nerve fibres) only in PDPN Q+SOC (p=0.003) and NPDPN Q+SOC (p=0.0005) groups. Pain relief in the PDPN Q+SOC
group was correlated with the increased PGP9.5 IENF (p=0.0008) and GAP43 (p=0.004), whereas those with lack of pain relief
showed no such increase; in some subjects pain relief and increased nerve fibres persisted over months. PGP9.5 IENF increase
correlated with axon-reflex vasodilatation in a NPDPN Q+SOC subset (p=0.006).
Conclusions: Capsaicin 8% patch can provide pain relief via nerve regeneration and restoration of function in DPN (disease
modification). It may thereby potentially prevent diabetic foot complications, including ulcers.
“disease modification”. We assessed whether Capsaicin 8% patch treatment can provide pain relief and also restore nerve density
and function via nerve regeneration, in both painful (PDPN) and non-painful (NPDPN) diabetic peripheral neuropathy.
Methods: 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.
Results: At 3 months after baseline, PDPN Q+SOC group had reduction in NPRS score (p=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 (p=0.02), and
correlated with reduction in SF-MPQ overall pain score (p=0.04). NPDPN Q+SOC group did not report pain during the entire study.
Density of intra-epidermal nerve fibres (IENF) with PGP9.5 was increased at 3 months in PDPN Q+SOC (p=0.0002) and NPDPN Q+SOC
(p=0.002) groups, but not in the PDPN SOC group. Increased sub-epidermal nerve fibres (SENF) were observed with GAP43 (marker
of regenerating nerve fibres) only in PDPN Q+SOC (p=0.003) and NPDPN Q+SOC (p=0.0005) groups. Pain relief in the PDPN Q+SOC
group was correlated with the increased PGP9.5 IENF (p=0.0008) and GAP43 (p=0.004), whereas those with lack of pain relief
showed no such increase; in some subjects pain relief and increased nerve fibres persisted over months. PGP9.5 IENF increase
correlated with axon-reflex vasodilatation in a NPDPN Q+SOC subset (p=0.006).
Conclusions: Capsaicin 8% patch can provide pain relief via nerve regeneration and restoration of function in DPN (disease
modification). It may thereby potentially prevent diabetic foot complications, including ulcers.
Date Issued
2022-10-26
Date Acceptance
2022-10-07
Citation
Frontiers in Neurology, 2022, 13
ISSN
1664-2295
Publisher
Frontiers Media
Journal / Book Title
Frontiers in Neurology
Volume
13
Copyright Statement
© 2022 Anand, Privitera, Donatien, Fadavi, Tesfaye, Bravis and Misra. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
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Sponsor
Diabetes UK
Grant Number
17/0005646
Subjects
1103 Clinical Sciences
1109 Neurosciences
1701 Psychology
Publication Status
Published
Article Number
ARTN 998904