Acupuncture for the Treatment of Itch: Literature Review and Future Perspectives

Abstract

Background: Chronic pruritus is a prevalent, multifactorial and debilitating condition that is often underestimated. This article reviews current evidence to evaluate the efficacy of acupuncture for the treatment of itch.

Results: Although many researchers have conducted observational studies, clinical trials, and systematic reviews on the subject, the lack of more-robust and well-designed studies to prove the effectiveness of acupuncture in the management of itch is evident. Many published studies are of poor quality, with no clear description of randomization methods, and an absence of control groups and measurable clinical outcomes. In addition, a lack of standardization in methods for assessing pruritus and the acupuncture treatment protocols hinders more-comprehensive and higher-quality pooled data analysis.

Conclusions: Current evidence cannot fully support acupuncture for the treatment of itch yet.

Introduction

Pruritus is considered chronic when it persists for more than 6 weeks.¹ It can be as debilitating as chronic pain, with important repercussions on the patient's quality of life (QoL).² Itching is a relatively frequent complaint: A large Norwegian study estimated that 8.4% of Oslo's population suffers from itching,³ whereas a German study identified a 13.5% prevalence of chronic itching in that general population.⁴ However, there is a lack of epidemiologic studies to corroborate these data. Pruritus is characteristic of several dermatologic conditions; a few include atopic dermatitis, psoriasis, lichen planus, and contact dermatitis. Itching can also be present in a variety of nondermatologic conditions, such as systemic diseases (e.g., cholestasis, renal failure, hyperthyroidism, and lymphoproliferative disorders), psychogenic disorders (e.g., delusional parasitosis and obsessive–compulsive disorders), and neuropathic disorders (e.g., notalgia paresthetica, meralgia paresthetica, and brachioradial pruritus). Despite its relevant impact and high prevalence rates, pruritus pathophysiology has only been elucidated partially due to its great complexity, and randomized controlled trials (RCTs) of various pharmacologic and nonpharmacologic treatments are still scarce.^1,5

Epidermal keratinocytes play an important role in inducing pruritus, either by producing mediators that bind directly to skin pruriceptors or by releasing various products that stimulate other cells to produce pruritogenic substances, such as neurotrophin-4, neural growth-factor (NGF), lipidic mediators, and endothelin-1. Among all the mediators known to induce itch, histamine, which is produced by mast cells, is probably the most widely studied. Histamine-induced pruritus occurs through H1 receptors in nerve fibers after mast-cell activation and degranulation. H4 receptors are also involved in inducing pruritus, while H3 receptors appear to be related to itch suppression.⁶ Other cells involved in pruritus induction are eosinophils, which might contribute to the high levels of NGF reported in the skins of patients who have atopic dermatitis⁷ and, therefore, have itching.

Once itch is triggered, its transmission to the central nervous system (CNS) occurs through unmyelinated type-C fibers, which may be histamine-independent or histamine-responsive,^6,8 reaching the dorsal horn of the medulla and ascending via the contralateral spinothalamic tract to the thalamus.^1,9 In the spinal cord, activation of gastrin-releasing peptide receptors (GRPRs) and the presence of substance P are important factors in the transmission of pruritus.^6,9 Pruritic-nerve stimulation activates multiple brain regions, such as the striatum and anterior insula (areas related to emotional salience, interoception, and motivational processing), putamen (region related to motivation and habitual behavior that could explain the urge to scratch),¹⁰ and the prefrontal cortex and premotor area (related to planning and execution of motor actions, such as scratching).¹¹

Many factors contribute to induction, exacerbation, or suppression of pruritus. Temperature, for example, can change the perception of itching—intense cold or heat reduce itch perception, while moderate cold increases that perception.¹² In addition, given that patients with chronic pruritus often have both peripheral and central neural hypersensitization, normally nonpruritogenic stimuli, such as human touch or friction with clothing, can be misinterpreted as itch triggers.^1,6 The presence of a painful counter-stimulus, most notably scratching or rubbing the skin, can suppress itch at least temporarily. Multiple theories have been proposed trying to explain suppression of pruritus by a counter-stimulus—one of the theories known as the “gate control” theory, suggests that pruritus can be suppressed at the spinal-cord level through mechanical or electrical stimuli transmitted by myelinated type-A fibers, favoring the transmission of painful sensations over itch.^6,9 There is also evidence to suggest the existence of an endogenous itch-modulation mechanism analogous to diffuse noxious inhibitory control (DNIC). Just as patients suffering from chronic pain have impaired functioning of DNIC, similarly, the same phenomenon occurs in patients suffering from chronic itching, possibly due to dysregulation of the pruritus-descending modulatory mechanisms.¹³

Multiple categories of topical and systemic medications have been described for treating pruritus. Topical agents include moisturizers, glucocorticoids, calcineurin inhibitors (e.g., tacrolimus), local anesthetics (e.g., capsaicin, lidocaine), coolants (e.g., menthol), and other new medications, such as cannabinoid agonists. Systemic medications involve the use of H1 antihistamines, anticonvulsants (e.g., gabapentin, pregabalin), mast-cell stabilizers, antidepressants (e.g., fluoxetine, mirtazapine, amitriptyline), μ-opioid antagonists (e.g., naltrexone, naloxone), κ-opioid agonists (e.g., nalfurafine hydrochloride), and even phototherapy.^1,5,6,14 One of the major challenges in clinical management of chronic pruritus is the patient's tolerability for the multiple side-effects of classic treatments. Prolonged use of topical corticosteroids, for example, may cause skin atrophy and telangiectasia. Chronic use of antihistamines, anticonvulsants, antidepressants, and opioid antagonists/agonists can lead to a number of adverse effects, such as drowsiness, lower limb edema, constipation, nausea and vomiting, and hepatotoxicity, among others.¹ Therefore, researchers have been increasingly seeking nonpharmacologic alternatives to manage pruritus, such as behavioral therapy and acupuncture.

ACUPUNCTURE MECHANISMS OF ACTION FOR TREATING PRURITUS

Acupuncture is an important part of Traditional Chinese Medicine (TCM) and an ancient technique dating back to the Neolithic Period in China ∼5000 years ago.¹⁵ Acupuncture involves insertion of needles in specific anatomical sites that may be located near the origin of the complaint or in distal portions of the body. After insertion and manipulation of the needle, it is common for the patient to report experiencing De Qi, which is characterized by pain, weight, numbness, or even paresthesia in the area near the insertion site.¹⁶

Zhang et al. hypothesized that mechanical stimuli due to needle insertion on acupoints could cause local degranulation of mast cells.¹⁷ As a result, release of histamine and several other bioactive substances from the degranulated mast cells granules could trigger a series of physiologic phenomena, including vasodilation at the needling site and pain modulation in the CNS.^17,18 An animal-model trial conducted by Huang et al. demonstrated that acupuncture's immediate effects are histamine-dependent through activation via H1 receptors of histamine-dependent fibers, thus generating an upstream signal and central pain neuromodulation.¹⁹ As acupuncture is a technique that can reduce certain types of chronic nociceptive pain at the peripheral and CNS levels, and given that pain and pruritus share some common neural receptors, mediators, and stimuli-transmission pathways,⁹ it is reasonable to suppose a theoretical basis showing that acupuncture also has a modulating effect on pruritus.²⁰

In 1987, Lundeberg et al. had already demonstrated the positive effects of acupuncture and intrasegmental electroacupuncture (EA) to treat experimentally induced pruritus with intradermal application of histamine in the upper limb.²¹ This antipruritic effect of acupuncture/EA when needles are applied to the same dermatome or areas adjacent to the itch-inducing site was studied further by Han et al. in 2008 based on an animal model using serotonin-induced itch in rats, with one possible explanation being the activation of κ-opioid receptors by needling.²² Pfab et al. have reported that, in patients who have atopic allergies, acupuncture is effective for decreasing basophil activation²³ and reducing type I hypersensitivity reactions,²⁴ suggesting an antiallergic effect in this subgroup of patients. A study by Napadow et al., using functional magnetic resonance imaging, revealed that acupuncture has the potential to reduce activation of the putamen, which is the brain region related to the motivation and habitual behavior behind the urge to scratch. That study also showed that acupuncture modulated the sensation of itch by reducing activation of the insula, striatum, and premotor cortex.¹¹

Another mechanism proposed to partially explain the effects of acupuncture on pruritus suppression is that needling alone already works as a counter-stimulus by modulating pruritus in the CNS.⁹ Moreover, it has been speculated that acupuncture needles activate type-C nerve fibers, encoding both pruritus and pain signals, which would lead to depletion of local neurotransmitters resulting in tachyphylaxis.²⁰

Acupuncture for the Treatment of Itch

Several studies have been performed to evaluate using acupuncture to treat pruritus. However, there is still a shortage of well-designed RCTs with adequate pharmacologic and placebo controls to determine the real efficacy of acupuncture for pruritus management. Another challenge is standardization of the itch-assessment method—although classically the visual analogue scale (VAS) is still the method of choice, this kind of scale does not take into account other subjective aspects of pruritus, such as impacts on sleep, anxiety/depression, or QoL. This is why many researchers have preferred other modalities that allow multidimensional assessment of pruritus such as the 5-D pruritus scale²⁵ or the Eppendorf itch questionnaire.²⁶

Upon reviewing the literature, it was not hard to perceive the heterogeneity of acupuncture regimens proposed to treat pruritus. There was great diversity in the choice of acupoints, although Qu Chi (LI 11) was the most-preferred site. Based on TCM theories, Quchi is quite versatile and can be used to disperse skin pathogenic factors. Other interesting acupoints for managing pruritus are Hegu (LI 4) for dispersing Damp-Heat accumulation of Wei (Stomach), Da Chang (Large Intestine), and Xiao Chang (Small Intestine), along with Quchi; Zusanli (ST 36) to invigorate Qi; and Xue Hai (SP 10), to activate Qi and promote Xue circulation.²⁷

A systematic review published in 2015 by Yu et al.¹⁰ demonstrated efficacy of acupuncture for treating pruritus with statistical significance, reporting a difference in mean pruritus intensity of 19.03 points (95% CI: 8.09–29.97; P = 0.0007) on the VAS, ranging from 0 to 100 points. However, this systematic review included only 3 RCTs, 2 of which evaluated pruritus in patients with atopic dermatitis and 1 study that enrolled patients with uremic pruritus, covering a total of only 70 patients. One trial in particular had an exceptionally small sample size of 10 patients randomized to verum acupuncture versus no treatment²³; therefore, the risk that the observed difference occurred by chance alone was substantial, although this was only a pilot trial designed to evaluate in vitro basophil CD63 expression better upon allergen stimulation in patients with atopic eczema and itch. In addition, none of the 3 studies compared an acupuncture-treated group with a control group receiving pharmacologic treatment—the control groups only received sham acupuncture or had no treatments at all. Although all of the studies applied therapeutic regimens including Quchi (LI 11), none of them had the same acupoint protocols.

In 2015, Tan et al.²⁸ conducted a systematic review to evaluate all of the existing literature on acupuncture for treating atopic dermatitis as a disease, not just to reduce its associated pruritus. No study in all of the evaluated research bases met the inclusion criteria of this systematic review, which revealed a knowledge gap, but the reviewers reported that several studies suggested an acupuncture role for reducing itch, which is one characteristic of the disease.

Kang et al.²⁹ conducted a preliminary clinical trial demonstrating the potential efficacy of acupuncture in the clinical management of symptoms of patients with atopic dermatitis, including pruritus, with statistical significance. In addition to pruritus, in both groups undergoing different acupuncture regimens, there was also improvement in several other outcomes such as the Scoring Atopic Dermatitis index, the Eczema Area and Severity Index, and the Dermatology Life Quality Index—indicators that are very important for assessing overall improvements in patients with atopy. As this was a preliminary study, the sample subjected to analysis was small (N = 28), thus the study lacked statistical power to support the study's results.

A systematic review published by Kim et al.³⁰ in 2010 researched studies that evaluated the efficacy of acupuncture for treating uremic pruritus. After including 6 studies with varied designs, such as RCTs, uncontrolled observational studies, and controlled clinical trials, the reviewers concluded that there was a lack of evidence to support the effectiveness of acupuncture for treating uremic pruritus.

A systematic review conducted by Simonsen et al.⁵ in 2017 to evaluate various treatment modalities for uremic pruritus included only 2 RCTs whose intervention was acupressure in its alternative therapies section. Both studies showed statistical significance in favor of acupressure, with a mean VAS (a 0–10-cm scale) after acupressure of 3.36 ± 2.37/3.84 ± 1.68 versus a mean VAS in the control groups of 5.08 ± 1.55/5.56 ± 2.28, respectively.

Another systematic review in 2018, by Malekmakan et al.,¹⁴ evaluating therapeutic options for uremic pruritus, included in its analysis only 1 study by Che-Yi et al.³¹ in the alternative therapies section, which happened to be the largest of the 3 RCTs included in the systematic review by Yu et al.¹⁰ (mentioned previously). This study assessed itch reduction in a total of 40 patients randomized into 2 groups (verum acupuncture versus sham acupuncture) using a questionnaire encompassing 3 domains: (1) severity; (2) distribution; and (3) presence of sleep disorders, totaling a maximum of 45 points. An acupuncture regimen, using the Quchi (LI 11) acupoint, was effective for reducing mean pruritus scores significantly from an average of 38.2 (standard deviation [SD] = 4.8) pretreatment to an average of 17.3 (SD = 5.5; P < 0.001) immediately after acupuncture, with a sustained response even after 3 months (mean score = 16.55; SD = 4.8; P < 0.001).

Discussion

Although many have conducted observational studies, clinical trials, and even systematic reviews on the subject, the lack of more-robust and well-designed studies to prove the effectiveness of acupuncture for managing itch is evident. Many published studies are of poor quality, with no clear descriptions of randomization methods, and absences of control groups and measurable clinical outcomes, which is why they were excluded from the analyzes of the previously mentioned systematic reviews. In addition to studies with larger numbers of participants for greater statistical power, more RCTs with subjects randomized to at least 3 groups (verum acupuncture as the intervention, and sham acupuncture and conventional pharmacological treatment as controls) should be performed—not only to prove efficacy, but also to determine the superiority or adjunctive action of acupuncture for treating chronic itching. Open studies provide almost no useful information for assessing therapeutic effects, given that van Laarhoven et al.³² demonstrated in a meta-analysis the considerable role placebo treatments in treating itch, thus implying the necessity of sham trials and the need for caution when analyzing positive reports of acupuncture's efficacy.

Another important issue is the need for further standardization of methods for assessing pruritus and the alternative treatment protocols based on TCM. The great heterogeneity in the scores and scales used as clinical outcomes and the lack of agreement in the choice of acupoints and even the TCM-based treatment methods (such as acupressure or auriculotherapy) undermine comparability between studies and preclude more-comprehensive assessments, such as meta-analyses, perpetuating this knowledge gap. The International Forum for the Study of Itch already published recommendations for assessing chronic pruritus in clinical trials, including several domains, such as pruritus intensity and course, anxiety and depression, sleep, health-related QoL, and scratching-associated lesions.³³ Nevertheless, no set of instruments is yet considered a consensus for assessing and acquiring data on chronic pruritus, although ongoing studies might provide a solution in the near future.

Conclusions

Chronic pruritus is a prevalent and debilitating condition that is often underestimated. Current evidence cannot fully support acupuncture, pharmacologic, and alternative therapeutic options for treating this condition yet. Continuing studies on the neuroendocrine mechanisms involved in transmission of itch to expand knowledge about itching's pathophysiology is of utmost importance, and further well-designed RCTs with statistical power to support or refute acupuncture as an option in the therapeutic arsenal for pruritus are required.

Author Disclosure Statement

No financial conflicts of interest exist.

Funding Information

No grant support was received for preparation of this review.

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CME Quiz Questions

Article learning objectives: After studying this article, participants should be able to describe current evidence on the efficacy of acupuncture for the treatment of pruritus, discuss some of the limitations of the scientific studies on acupuncture and pruritus, and summarize the author's recommendations for future research on acupuncture and pruritus.

Publication date: April 16, 2021

Expiration date: April 30, 2024

Disclosure Information:

Authors have nothing to disclose.

Richard C. Niemtzow, MD, PhD, MPH, Editor-in-Chief, has nothing to disclose.

Questions:

• 1. As described in the article, one of the major challenges in the clinical management of chronic pruritus is the multiple side effects of commonly used treatments. Which of the following best describes how the authors determined this conclusion?

  • a. There is increasing interest in the ways in which pruritus has been managed historically in non-western cultures.
  • b. There is a renewed focus on phytomedicine solutions based upon indigenous uses around the globe.
  • c. Researchers are increasingly seeking non-pharmacological alternatives for the management of pruritus such as behavioral therapy and acupuncture.
  • d. Pharmacologic research is investigating paired therapies in which dual pharmaceutical agents can be prescribed together in which one agent counteracts the side effects of the main agent.
  • e. Current research on pruritus is investigating the application of nanotechnology in drug delivery to reduce side effects.
• 2. According to the authors, gate-control theory suggests that the suppression of pruritus by a counter-stimulus (scratching) occurs by suppression of itch sensation at the spinal cord level through mechanical or electrical stimuli transmitted by myelinated type A fibers. Based upon this, which of the following best describes the authors' proposal based on this?

  • a. Novel methods of counter-stimulus need to be investigated in order to decrease the dependence upon topical pharmaceutical agents such as corticosteroids.
  • b. As acupuncture is a demonstrated method of improving chronic nociceptive pain, and since pain and pruritus share some common neural receptors and transmission pathways, acupuncture may have a similar modulating effect on pruritus.
  • c. Topical corticosteroids have been demonstrated to decrease transmission of itch sensation by inhibition of unmyelinated C fibers.
  • d. Further research into the brain regions related to motivation and habitual behavior such as scratching.
  • e. Consensus recommendations from the International Forum for the Study of Itch (IFSI) be instituted in study protocols.
• 3. The authors review a number of acupuncture studies which demonstrate a beneficial effect on pruritus. Which of the following is from the authors after reviewing the studies?

  • a. Pfab et al. demonstrated that in atopic dermatitis patients acupuncture was effective in decreasing basophil activation and reducing type-1 hypersensitivity reactions.
  • b. Han et al. reported that in a narcotic dependent population undergoing monitored rehabilitation, acupuncture decreased narcotic withdrawal associated pruritus.
  • c. Base et al. reported that acupuncture decreased opioid induced itching.
  • d. Napadow et al. reported that fMRI imaging revealed that acupuncture increased the activation of the putamen, the brain region related to habitual behavior such as scratching.
  • e. Zhang et al. hypothesized that mechanical stimuli due to needle insertion on acupoints could inhibit local degranulation of mast cells.
• 4. The authors discuss that in the clinical studies on pruritus there is a great diversity in the choice of acupoints. According to the authors, which is the most commonly utilized acupoint in these studies?

  • a. Du 14 Dazhui
  • b. BL 12 Fengmen
  • c. GB 31 Fengshi
  • d. LI 11 Quchi
  • e. GB 20 Fengchi
• 5. The authors discuss Yu et al.'s 2015 systematic review on acupuncture and itch which showed acupuncture to be efficacious in treating pruritus with statistical significance. Which of the following is true about this study?

  • a. This study cannot be considered conclusive because it included only three RCTs and included a low overall total number of patients. In general, more robust and well-designed studies are needed on the effectiveness of acupuncture for management of itch.
  • b. Yu's study conclusively proves acupuncture's benefit in treating several types of pruritus.
  • c. Yu's study could be improved by including studies that utilized Zelen design.
  • d. Yu's study demonstrates that health related quality of life questions are not necessary in this topic of study.
  • e. Yu's study demonstrates that there is now a consensus on a set of instruments for assessing and acquiring data on chronic pruritus.

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