Therapeutic and experimental therapeutic studies on acupuncture and itch: review of the literature.

Itch accompanies most inflammatory skin diseases but may occur as a solitary sensation in otherwise normal skin. Chronic itch often requires combined treatments but some cases remain therapy resistant. Complementary medicine is becoming increasingly popular among patients. Acupuncture is the oldest and most well-studied alternative option with evidence-based effect on pain. This article summarizes the rational for the use of acupuncture in treatment of itch and reviews therapeutic and experimental therapeutic studies on acupuncture and itch.

Cutaneous innervation before and after one treatment period of acupuncture.

BACKGROUND: The effect of acupuncture on nociceptive pain is well documented, but effects on nociceptive itch have been contradictory. OBJECTIVES: To evaluate possible effects of acupuncture on the occurrence, distribution and function of sensory nerve fibres in human skin. METHODS: Ten subjects were treated by inserting 10 acupuncture needles subcutaneously at the upper lateral aspect of one buttock. The subjects were recruited from an acupuncture clinic and were undergoing specific acupuncture treatment for their disorders. The needles were stimulated (rotated to and fro) twice during the twice-weekly 25-min sessions over 5 weeks. Skin biopsies, diameter 3 mm, were taken before and 3-6 days after local acupuncture. Antibodies to the pan-neuronal marker protein gene product 9.5 (PGP 9.5), calcitonin gene-related peptide (CGRP), vanilloid receptor 1 (VR1) and mu- and delta-opioid receptors were employed to study sensory unmyelinated nerve fibres that transmit nociceptive pain and itch. A histamine prick test using planimetry was used to record experimental itch after acupuncture on the treated area and on the corresponding control skin, and a visual analogue scale was used to evaluate itch. RESULTS: The mean +/- SEM number of CGRP-immunoreactive nerve fibres per biopsy section was reduced from 36.0 +/- 3.3 to 21.3 +/- 4.0 (P = 0.05) after the treatment. PGP 9.5-immunoreactive nerve fibres were found both in the epidermis and in the subpapillary dermis. The mean +/- SEM total number of PGP 9.5-immunoreactive nerve fibres decreased from 249.8 +/- 16.7 to 211.8 +/- 12.0 (P = 0.03). The PGP 9.5-immunoreactive nerve fibres occurring in the dermis appeared more fragmented after the acupuncture compared with pretreatment. VR1 immunoreactivity was found both in the free nerve fibres and in kite-like formations, possibly mast cells, throughout the dermis, sometimes occurring around hair follicles. The mean +/- SEM number of VR1-immunoreactive elements was not significantly influenced by acupuncture, at 33.5 +/- 4.6 vs. 43.0 +/- 4.4 (P = 0.09). No immunoreactivity was found in the skin against mu- and delta-opioid receptors with the antibodies used in this study. Neither histamine-induced itch nor cutaneous responses were influenced by acupuncture. CONCLUSIONS: The present data indicate an effect of acupuncture on neuropathic itch but not histamine-mediated itch. Our findings support the opinion that the pain-relieving effects of acupuncture partly depend on its effect on the peripheral innervation.

Circulating eosinophils in asthma, allergic rhinitis, and atopic dermatitis lack morphological signs of degranulation.

BACKGROUND: In allergic diseases, eosinophils in affected tissues release granule proteins with cytotoxic, immunoregulatory, and remodelling-promoting properties. From recent observations, it may be assumed that eosinophils degranulate already in circulating blood. If degranulation occurs in the circulation, this could contribute to widespread systemic effects and provide an important marker of disease. OBJECTIVE: To determine the degranulation status of circulating eosinophils in common allergic diseases. METHODS: Using a novel approach of whole blood fixation and leucocyte preparation, the granule morphology of blood eosinophils from healthy subjects, non-symptomatic patients, symptomatic patients with asthma, asthma and Churg-Strauss syndrome, allergic rhinitis, and atopic dermatitis was evaluated by transmission electron microscopy (TEM) and eosinophil peroxidase (TEM) histochemistry. Plasma and serum levels of eosinophil cationic protein were measured by fluoroenzymeimmunoassay. Selected tissue biopsies were examined by TEM. RESULTS: Regardless of symptoms, circulating eosinophils from allergic patients showed the same granule morphology as cells from healthy subjects. The majority of eosinophil-specific granules had preserved intact electron-density (96%; range: 89-98%), while the remaining granules typically exhibited marginal coarsening or mild lucency of the matrix structure. Abnormalities of the crystalline granule core were rarely detected. Furthermore, granule matrix alterations were not associated with any re-localization of intracellular EPO or increase in plasma eosinophil cationic protein. By contrast, eosinophils in diseased tissues exhibited cytolysis (granule release through membrane rupture) and piecemeal degranulation (loss of granule matrix and core structures). CONCLUSION: In symptomatic eosinophilic diseases, circulating blood eosinophils retain their granule contents until they have reached their target organ.

Cutaneous field stimulation of sensory nerve fibers reduces itch without affecting contact dermatitis.

BACKGROUND: A new technique, cutaneous field stimulation (CFS), which activates electrically unmyelinated C-fibers, is used to treat localized itch. Its action is similar to that of capsaicin, the pungent agent in hot peppers, which enhances delayed allergic reactions. The aim of the study was to investigate how experimental contact dermatitis responds to CFS. METHODS: Twelve patients with contact dermatitis in response to nickel were treated by CFS for 1 h each for four consecutive days. A flexible plate containing electrodes was applied to a test area on the upper arm and was stimulated by a constant current (0.8 mA). On the fifth day, patients were provoked by epicutaneous application of nickel sulfate (allergic contact dermatitis) and benzalkonium chloride (irritant contact dermatitis), and by intradermal tuberculin (delayed immunologic reaction). Twelve other patients with IgE-mediated allergy were treated by CFS on the lower arm for 1 h and were then pricked with histamine and allergen extracts (wheal volume was measured) and were tested using benzoic acid (nonimmunologic contact urticaria; closed test). Ten of these patients were also treated by CFS for four days, and experiments were performed on the fifth day. RESULTS: Test reactions to nickel, benzalkonium, and tuberculin were found to be unaffected by CFS treatment. Although allergic prick test reactions were enhanced (by 28%) after a single CFS treatment, the associated itch was significantly reduced both after single and repeated CFS treatments (by 65% and 38%, respectively). CONCLUSIONS: Repeated use of CFS to reduce itch has no adverse effects on contact dermatitis.

Cutaneous field stimulation in the treatment of severe itch.

OBJECTIVE: To evaluate the efficacy of cutaneous field stimulation of C fibers for the treatment of itchy skin and its effect on peripheral nerve fibers as shown in skin biopsy specimens. DESIGN: We conducted an open-label uncontrolled study of 19 patients with itching. Each patient applied a flexible plate containing electrodes to the itchy area for 20 minutes at a time once daily for 5 weeks to stimulate nerve fibers with a constant current (0.8 mA). Skin biopsy specimens were collected before treatment and at the end of treatment and were immunostained for calcitonin gene-related peptide and protein gene product 9.5. SETTING: University hospital in Lund, Sweden. PATIENTS: Sixteen patients with nostalgia paresthetica or brachioradial pruritus and 3 with generalized itch. INTERVENTIONS: Cutaneous field stimulation and punch biopsies of the itchy skin. MAIN OUTCOME MEASURES: Visual analog scale for assessment of itching and counting the immunoreactive nerve fibers in 3-mm biopsy specimens. RESULTS: Patients with localized itching experienced a reduction in mean values on the visual analog scale (from 78% before treatment to 42% by the end of the fifth week). The number of protein gene product 9.5- immunoreactive nerve fibers in the epidermis was reduced by 40% by the end of treatment compared with baseline values. CONCLUSIONS: Cutaneous field stimulation is an effective alternative for the treatment of localized itching. The reduction in itching is accompanied by degeneration of the epidermal nerve fibers, as evidenced by the loss of protein gene product 9.5 immunoreactivity.

Dual effects of CGRP-antagonist on allergic contact dermatitis in human skin.

There is increasing evidence of an interaction between the nervous and the immune systems. The aim of this study was to investigate the rôle of calcitonin gene-related peptide (CGRP) in the modulation of the elicitation of immediate and delayed, immunological and non-immunological reactions in human skin. CGRP (13 pmol and 39 pmol), and the CGRP-antagonist, CGRP/8-37/, (50 pmol and 500 pmol) were injected intracutaneously prior to provocation tests. Patients with allergy to nickel were provoked with nickel sulfate epicutaneously, and the reactions were evaluated by a clinical scoring system (guidelines of the International Contact Dermatitis Research Group). Patients with allergy to birch pollen were provoked by a prick test with the allergen, and the volume of the weals was measured. The patients were also provoked with tuberculin (delayed immunologic reaction), benzalkonium chloride (irritant contact dermatitis), UV-light and benzoic acid (non-immunologic contact urticaria). The test reactions were estimated by planimetry. CGRP/8-37/ exerted dual effects on allergic contact dermatitis, causing potentiation at a dose of 500 pmol (p= 0.004) and inhibition at a dose of 50 pmol (p=0.012). Other reactions were not significantly affected by the pretreatments. The results suggest that CGRP participates in delayed inflammatory reactions, but is not involved in immediate immunologic reactions.