Rational treatment of chemotherapy-induced peripheral neuropathy with capsaicin 8% patch: from pain relief towards disease modification

Figures & data

Figure 1 Study flow diagram.

Abbreviations: NCS, nerve conduction study, PGIC, patient global impression of change.

Table 1 Patients’ demographics and clinical characteristics

Patients demographics
Age (years, range)	64 (45–79)
Number of patients	16
Number of male patients (%)	8 (50)
Ethnic origin, %
Asian or Asian British	25.0
Caucasian  Other	68.0 7.0
Clinical characteristics
Duration of CIPN (years, range)	2.5 (5 month-8 years)
Pain level at baseline (NPRS, mean [SEM])	6.6 (0.43)
Number of patients taking pain medications at baseline	12 (75%)
Acetaminophen (Paracetamol)   Gabapentinoids (Pregabalin and Gabapentin)	2 4
Tricyclic anti-depressants/SNRIs   Opioids   Other analgesic combinations	1 4 1
Patient cancer types:  Colon cancer  Multiple myeloma  Lung cancer  Ovary cancer	7 6 1 2
Patient chemotherapy types:  Bortezomib  Platinum/taxane or both	6 10

Abbreviations: CIPN, chemotherapy-induced peripheral neuropathy; SEM, standard error of the mean; SD, standard deviation; NPRS, numerical pain rating scale; SNRIs, serotonin and norepinephrine reuptake inhibitors.

Table 2 Results before and after capsaicin 8% patch: spontaneous pain (NPRS), short form McGill pain questionnaire, patient global impression of change, quantitative sensory testing, and contact heat evoked potentials

Numerical Pain Rating Scale (NPRS), mean ± SEM
	Pre patch application	Post patch application	p-value
Spontaneous pain Light touch evoked pain Cold evoked pain	6.6±0.4 4.8±0.8 4.0±0.8	5.3±0.5 2.6±0.7 2.6±0.8	0.01 0.02 0.03
Short Form McGill pain Questionnaire (SFMPQ), mean ± SEM
	Pre patch application	Post patch application	p-value
Continuous pain Intermittent pain Affective pain Neuropathic pain Overall pain	27.9±3.6 21.2±3.8 9.5±2.8 30.5±3.3 83.6±12.3	14.9±2.9 14.0±3.1 9.4±2.4 19.5±2.6 53.5±8.7	0.001 ns ns 0.0007 0.003
Patient Global Impression of Change (PGIC), mean ± SEM
	Pre patch application	Post patch application	p-value
PGIC score	4.2±0.2	2.8±0.3	0.003
Quantitative Sensory Testing (QST), mean ± SEM
	Pre patch application	Post patch application	p-value
Cool Threshold (°C) Warm Threshold (°C) Cold Pain Threshold (°C) Heat Pain Threshold (°C) Vibration Threshold (V) Monofilament Threshold (gm)	20.4±2.1 44.3±1.2 9.6±2.1 47.9±0.7 33.6±3.4 34.9±22.2	20.7±1.7 43.9±0.9 10.4±2.4 48.2±0.6 28.7±3.0 2.3±1.4	ns ns ns ns ns ns
Neuropathy Impairment Score Lower Limbs (NIS-LL), mean ± SEM
	Pre patch application	Post patch application	p-value
NIS-LL Score	10.5±1.2	8.6±0.8	0.01

Abbreviations: SEM, standard error of the mean; NPRS, numerical pain rating scale; ns, not significant; PGIC, patient global impression of change; QST, quantitative sensory testing; NIS-LL, neuropathy impairment score lower limbs; °C, Celsius degree; V, Volt; gm, gram.

Figure 2 Immunohistochemistry in skin biopsies for PGP9.5, before and after capsaicin 8% patch treatment. Intra-epidermal nerve fibers (arrowed) and sub-epidermal nerve fibers from (A) control subjects, at the baseline visit (B, Q PRE) and, after capsaicin 8% patch treatment (C, Q POST), magnification x40. (D) Bar chart of intra-epidermal nerve fibers for PGP 9.5 counts, (E) bar chart of sub-epidermal (SENF) analysis (% area).

Notes: *Significant; **very significant.

Figure 3 Immunohistochemistry in skin biopsies for TRPV1, before and after capsaicin 8% patch treatment. Intra-epidermal nerve fibers (arrowed) and sub-epidermal nerve fibers from (A) control subjects, at the baseline visit (B, Q PRE) and, after capsaicin 8% patch treatment (C, Q POST), magnification x40. (D) Bar chart of intra-epidermal nerve fibers for TRPV1 (IENF) counts; (E) bar chart of sub-epidermal (SENF) analysis (% area) for TRPV1.

Notes: *Significant; **very significant.

Figure 4 Immunohistochemistry in skin biopsies for SNSR, before and after capsaicin 8% patch treatment. Intra-epidermal nerve fibers (arrowed) and sub-epidermal nerve fibers from (A) control subjects, at the baseline visit (B, Q PRE) and, after capsaicin 8% patch treatment (C, Q POST), magnification x40. (D) Bar chart of intra-epidermal nerve fibers for SNSR (IENF) counts; (E) bar chart of sub-epidermal (SENF) analysis (% area) for SNSR.

Note: *Significant.

Figure 5 Immunohistochemistry in skin biopsies for GAP43, before and after capsaicin 8% patch treatment. Representative image of intra-epidermal nerve fibers (arrowed) and sub-epidermal nerve fibers from (A) control subjects, at the baseline visit (B, Q PRE) and, after capsaicin 8% patch treatment (C, Q POST), magnification x40. (D) Bar chart of intra-epidermal nerve fibers for GAP43 (IENF) counts; (E) bar charts of sub-epidermal (SENF) analysis (% area) for GAP43.

Notes: *Significant; **very significant.

Figure 6 Immunohistochemistry in skin biopsies for NGF, before and after capsaicin 8% patch treatment. NGF immunostaining of basal epidermis in calf skin obtained from (A) control subjects, and CIPN patients before (B, Q PRE) and after capsaicin 8% patch treatment (C, Q POST), magnification x40. (D) Bar chart showing the basal cell NGF image analysis (% area).

Notes: *Significant; **very significant.

Figure 7 Immunohistochemistry in skin biopsies for NT3, before and after capsaicin 8% patch treatment. NT3 immunostaining from (A) control subjects, and CIPN patients before (B, Q PRE) and after capsaicin 8% patch treatment (C, Q POST). (D) Bar chart showing NT3 suprabasal image analysis (% area).

Notes: *Significant; **very significant.

Figure 8 Immunohistochemistry in skin biopsies for Langerhans cells (LCs), before and after capsaicin 8% patch treatment. LCs immunostaining in the epidermis of calf skin from (A) control subjects, and CIPN patients before (B, Q PRE) and after capsaicin 8% patch treatment (C, Q POST), magnification x40. (D) Bar chart showing LCs image analysis (% area).

Note: **Very significant.