Hypericum perforatum to improve post-operative Pain Outcome after monosegmental Spinal microdiscectomy (HYPOS): a study protocol for a randomised, double-blind, placebo-controlled trial

Disc herniation is one of the most common degenerative diseases of the lumbar spine. The incidence for lumbar disc herniation in Germany is 150/100,000 people per year. Sixty out of those 100,000 patients undergo intervertebral disc surgery, resulting in 50,000 operations a year [1]. The prevalence of a herniated disc is estimated to be 20–30% for the age group between 35 and 64 years. In a review of the prevalence of degenerative lumbar disc lesions, Battié et al. reported frequencies for a reduced disc height of 3–56% and for lumbar herniation of 3–63% depending on the design of the study [2]. Moreover, it was noted that only very few studies investigated the frequency of disc herniation with segment-related radiculopathy at all. The results show that the frequency for this incident is in the low single-digit range [3].

Treatment options for a lumbar disc herniation are determined by the duration and presence of the symptoms and the severity of the resulting pain. Besides, the nature of the symptoms (such as weakness or numbness), the patient’s age and further progression of pain relief are important decision-making parameters for conservative therapy or surgery [4]. If medication, physical therapy, and/or other non-surgical treatments have not led to a significant symptom improvement over 6 weeks, a relative indication for surgery is given [4]. Patients who undergo lumbar surgery as well as patients who are not operated on both improve within 2 years. However, there is a trend with regard to pain reduction in favour of patients who undergo lumbar disc herniation surgery [5]. This is underpinned by the 4-year results of the Spine Patient Outcomes Research Trial (SPORT) which showed significantly better results in the pain scores in surgical patients compared to the conservatively treated group [6].

Depending on the main diagnosis, in 2010, patients with lower back problems were subjected to back surgery in 38% of the cases [7]. Since the introduction of the Diagnosis Related Groups (DRG), the length of stay in Germany after minimal invasive surgery is about 3–4 days if no adverse events (AEs) occur, which is comparable with international data [8].

For the feasibility and the course of mobilisation and rehabilitation, post-surgical pain management plays a crucial role [9]. The post-surgical phase requires adequate pain therapy according to the World Health Organisation (WHO) analgesic ladder. Non-opioid analgesics (ibuprofen, diclofenac, novaminsulphon, step 1) and weak opioids (tilidine or tramadol, step 2) are most commonly used. Only in very rare cases are strong opioids (step 3) applied [4, 10]. Because of possible side effects, i.e. gastrointestinal pain, sedation, peptic ulceration, allergy and rash, respiratory depression, nausea and vomiting, rash and urinary retention, the choice of the non-steroidal anti-inflammatory drugs (NSAIDs) and opioids must be individually tailored to the patient, aiming to control inflammation and its consequent pain [9‐12].

At the Community Hospital Herdecke, Germany, homeopathic remedies are also offered in addition to the standard treatments mentioned above on patient request [13]. Homeopathy is one of the oldest traditional European medical systems founded by the German physician Samuel Hahnemann (1755–1843) in 1796. It is based on ‘the principle of similars’ already described in ancient Greek sources of medicine. According to the ‘like cures like’ principle of healing, diluted substances that cause symptoms in healthy individuals can be used to treat patients with similar symptoms [14]. A homeopathic remedy is made by a process of dilution and succession. They are named by their grade of dilution as decimal (D), centesimal (C) or quinquagintamillesimal (Q or LM) potencies [15]. Thus, a dilution of D6 indicates that the original substance is diluted by a factor of 10^-6, while a dilution of C30 denotes a dilution of 100^-30 [16]. Homeopathic remedies can be prescribed individually, but patients are often treated with typical remedies that have shown to be effective according to clinical experience, irrespective of the individuality of a given patient [17]. This idea of the concept of ‘proven indications’ was made famous by the Austrian physician Mathias Dorcsi in the twentieth century [18].

From a homeopathic perspective, the administration of Hypericum perforatum is indicated in order to improve wound healing and reduce repeatedly occurring neural pain [19, 20].

H. perforatum (St. John’s wort) is a member of the Guttiferae family with about 400 known species of Hypericum in Europe and is one of the oldest medical plants with a history of more than 2000 years. It grows in sunny locations with well-drained, limey soil and reaches a height of 50 to100 cm. Yellow star-shaped flowers, often clustered in a trio, have five petals and the leaves contain tiny, transparent oil glands resembling perforations [21].

Experimental studies have demonstrated that the administration of potentiated Hypericum can lead to a reduction of symptoms due to spinal disc pathology and associated pain caused by a pinched and irritated nerve [22]. In clinical trials the pain-reducing effect of Hypericum could also be observed in a number of studies, amongst others in neuropathic pain [23‐25], after reconstruction of knee ligaments [26], or after tooth extraction [21]. However, this effect was only shown in combination with other homeopathic remedies. The question to what extend the results shown in these studies can be attributed to the specific effects of Hypericum have not been resolved so far. The adjuvant administration of Hypericum for the present indication of post-surgical pain after lumbar microdiscectomy surgery has not been investigated within the framework of a scientific clinical setting.

Despite the fact that homeopathy has a long tradition in the complementary treatment of patients and is part of the medical curriculum in many European universities [37] there is an ongoing debate on its effectiveness and credibility. Thus, more robust clinical studies with clear and relevant endpoints are needed to substantiate the evidence base from primary to critical care.

This study evaluates the application of highly diluted Hypericum in a randomised controlled trial compared to placebo for the first time. The prescription of homeopathic Hypericum for pain conditions is historically well established and respective publications can be traced back to the medieval age [38]. In the field of homeopathy, Kent, the founder of American homeopathy, in his lectures on homeopathic Materia Medica states: ‘One who makes a study of the proving of Hypericum will be reminded of a class of injuries involving sentient nerves and it is not surprising that this remedy has come into use for the results of such injuries’ [39].

Neural pain after surgery caused by damage or injuries of the nerves often develops into stabbing and unbearable pain. Management of such post-surgical pain conventionally includes the application of opioids in varying dosage, codeine, dihydrocodeine, tilidine, naloxone or tramadol. If necessary, opioids are combined with peripheral pain-relieving medication or substances like gabapentin or pregabalin. As opioids are associated with a variety of potential side effects, including respiratory depression, homeopathic Hypericum is a promising additional treatment option in multimodal pain management, even though its effectiveness still has an insufficient evidence base [38]. Our study, therefore, may be seen as a first step towards providing clinical evidence. To ensure the quality of the study, its reliability and validity, the study protocol is based on the Consolidated Standards of Reporting Trials (CONSORT) guidelines and the SPIRIT guidance for clinical trials [40, 41]. If necessary, CONSORT extensions (i.e. for pragmatic randomised trials) will be considered in the final reporting of the study. Moreover, the checklists of Bornhöft et al. 2006 [42] and Mathie [43] for model validity of homeopathic treatment (MVHT) have been applied to obtain a broad acceptance of the study results.

This study makes use of a non-individualised classical homeopathic approach. Other researchers decided to make use of a complex homeopathic approach, i.e. in the treatment of low back pain due to osteoarthritis [44] or an individualised approach, i.e. in the pain management in osteoarthritis of the knee [45].

Our decision to apply only one remedy is based on the concept of ‘homeopathically proven indications’ where injuries are treated with typical remedies that were shown to be effective irrespective of the individuality of a given patient [17]. As Hypericum is known as a remedy for stabbing pain, especially when nerve root irritation or nerve damage is involved, we decided to apply Hypericum C200 as a sole remedy for this condition.