External application of Chinese medicine formula combined with analgesic drugs to treat lung squamous cell carcinoma pain:A case study with mixed methods

Hong Chen,Jun-Qiang Zhao,Yun-Lan Jiao,Dou Wang,Yu-Fang Hao*

1Beijing University of Chinese Medicine Dongfang Hospital,Beijing,China.2School of Nursing,Beijing University of Chinese Medicine,Beijing,China.

#Co-first author

Abstract Objective:To investigate the effectiveness of the external application of Chinese medicine combined with analgesic drugs to treat lung squamous cell carcinoma pain.Methods:A 54-year-old patient with upper lobe of the left lung squamous cell carcinoma was studied,who suffered from severe cancer pain with the initial numeric rating scale(NRS)7 point when adm itted.Exterior-use formula was applied to pain spot to relieve the pain.M ixed methods approach comprising NRS,Short-form of McGill Pain Questionnaire,quality of life scale,times of breakout pain,records of adverse reactions and sem i-structured interviews were utilized to evaluate the effect.Results:With the combination use of the formula and analgesic drugs,the patient’s NRS score dropped from 7 to 3 point.Quality of life scale score improved from 33 to 42 point.Times of breakout pain reduced from twice to none.The amount of oxycodone decreased from 30 mg Bid to 10 mg Bid.No adverse effect appeared.The patient’s felt more energetic with good sleep and appetite.Conclusion:This formula is effective and safe for pain relief when combined with analgesic drugs,and may be a good option in dealing with local cancer pain.Future random ized,controlled studies are needed to better evaluate the efficacy.

Keywords:Cancer pain,Chinese medicine,Case study,M ixed methods

Background

Cancer pain is one of the most common and most unbearable symptoms in patients with malignant tumors,which seriously affects patients’quality of life(QoL).Survey has shown that in China 51%to 61.6%patients with malignant tumors suffer from cancer pain[1].The WHO three-step analgesic principle has become globally recognized as an efficient way to control this type of pain,nevertheless patients taking painkillers often manifest with various adverse reactions,like constipation,nausea,sweating,peptic ulcer etc.,which obviously torture patients physically and mentally[2].

Chinese medicine,with its unique theoretical system in cancer treatment,has come up with diversified approaches to tackle cancer pain,like oral administration or external application of Chinese medicine,acupuncture and so forth,and has got great achievements in this field.In those treatment approaches,the external application of Chinese medicine has gradually received global attention for its exceptional advantage in relieving cancer pain[3].External treatment therapy is an indispensable branch of Chinese medicine,and is featured by its unique curative effect in the treatment of cancer pain[4].By applying Chinese medicine to the skin directly,the medicine can penetrate through skin or mucosa to the pain spot,and help to relieve pain quickly and effectively.If combining with analgesic drugs,it can improve the clinical efficacy,reduce the dosage of analgesic drugs and decrease the occurrence of adverse reactions,especially for those with severe cancer pain[5].External treatment therapy is simple,safe and convenient,especially for the localized focus and superficial cancer spot.Our hospital has made great progress in cancer pain treatment with empirical formula.A specific case will be presented as follows to witness its effectiveness.

M aterials and Methods

Patient

M r.Li,male,54 years old,chief complaint:left lung bump for 11 months,interm ittent fever for 3 months.History of present illness:in October 2015,the patient was tested with a chest CT due to cough and expectoration.CT showed a left upper lobe space occupying lesion,a bronchoscopy was carried out to this patient afterwards,which indicated squamous cell carcinoma.This patient was then admitted to one tertiary hospital in Beijing City for treatment.Since the chest CT showed mediastinal and hilar lymphadenectasis(lymph node enlargement)and group emergence,the patient was diagnosed with upper lobe of the left lung squamous cell carcinoma with no radical resection after being consulted by thoracic surgeon.Until 10th March,2016,the patient had received combined chemotherapy with docetaxel and cisplatin for a total of 4 cycles.Since the beginning of June,the patient started the radiotherapy for a total of 30 times.At the late stage of chemotherapy and radiotherapy,the patient suffered interm ittent fever and had improved after anti-infection therapy.This patient was admitted to our hospital on18th September,2016.Symptom:interm ittent fever with the highest temperature of 39.3°C,cough with expectoration,chest tightness after exercise,hypochondriac pain in both sides of ribs with left side more obvious,numeric rating scale(NRS)6 points,fatigue,low temperature in the limbs,chills,poor sleep,normal urination,difficult defecation with every 3 to 4 days.Physical exam ination:rough breath sounds in both lungs,low breath sounds in the left lung,wheeze in both lungs.This patient has past history of hypertension.Western medicine diagnosis for admission was left upper lobe lung squamous cell carcinoma with lung infection;Chinese medicine diagnosis was pulmonary carcinosis,impairment of the yang principle,phlegm and blood stasis.The patient was treated with anti-infection drugs-vancomycin,meropenem;ambroxol,and dyphylline to relieve cough and reduce sputum.Oxycodone hydrochloride was also given 20 mg bid Po.After 10 days’consecutive treatment,the patient’s body temperature went back to 36.7°C.Symptoms of cough and expectoration were eased,but hypochondriac pain in both sides of ribs were getting worse than before with NRS 7 points,poor sleep,defecate once in 4 days.Taking into account that the oxycodone dosage increment might result in more severe constipation and gastrointestinal symptoms,we gave patient the external application of Chinese medicine with characteristics of our own department to cope with the cancer pain.The patient suffered from hypochondriac pain with fixed pain spot and felt better with warm or pressure on pain spot.Pain aggravated by cold and relieved by warm th.Those symptoms indicated that it belonged to “Yin Syndrome”category in Chinese medicine local syndrome differentiation and should be treated with the principle of warming Yang and dispelling cold,removing toxin and resolving stasis,dredging collaterals and relieving pain.The external application formula was:Rougui(Cinnamom i Cortex)18 g,Dingxiang(Caryophylli Flos)30 g,Banxia(Pinelliae Rhizoma)27 g,Chuanshanjia(Manis Squama)30 g,Xiangfu(Cyperi Rhizoma)30 g,Zhiqiao(Aurantii Fructus)30g,Xiebai(A llii Macrostemonis Bulbus)45 g,Heshouwu(Polygoni Multiflori Radix)18 g,Quanxie(Scorpio)18 g.

Operation steps

Preparation of exterior-use ointment:Grinded the above drugs into powder;added liquor 10 ml,honey 10 ml,ginger juice 6 ml,sesame oil 5 ml;mixed all the ingredients well and made into paste.Folded the gauze into a cross and took out the mixed medicine onto the gauze with a scoop.Stacked up the gauze in turn to cover the medicine.A fter that,rolled the medicine into a pie plaster with diameter 10 cm and thickness 5 mm.Heated the plaster in a microwave oven with high-heat for 5 seconds.

Usage method:Cleaned the skin of the pain spot with warm water;applied the prepared plaster onto both sides of the ribs.The application time started from 9:00 am and lasted for 4 hours,once daily.

M easurements

Quantitative methods.Pain intensity assessment:NRS was used to evaluate pain relief daily.The degree of pain would be presented in numbers 0-10,0 indicates no pain,and 10 represents the most severe pain.Short-form of McGill Pain Questionnaire(SF-MPQ)[6]:it comprises of 15 descriptors(11 sensory descriptors and 4 affective descriptors)rated on an intensity scale as 0=none,1=m ild,2=moderate,3=severe.The SF-MPQ also includes the Present Pain Intensity index and a visual analogue scale.

QOL evaluation:Refer to the QOL scale in medical book “Oncology nursing(new edition)”2011[1].The full score is 60.Very poor QOL(＜20 points),poor QOL(20-30 points),general QOL(31-40 points),good QOL(41-50 points),very good QOL(51-60 points).

Records of adverse reactions:Reference to the United States NCI adverse reaction classification criteria.

Times of breakout pain and dosage of Oxycodone were also recorded.

Qualitative method.Sem i-structured interviews were conducted to this patient on the 1st,7th and 14th day after the initial external application of this formula.The interview guide included the following key domains:1)what is the pain like?2)What has this pain affect the daily life(sleep,appetite,daily activity etc.)?Each interviewlasted about 10 to 15 minutes and was audio-taped.Notes were also taken where key information appeared.The interviews were transcribed verbatim in Chinese within 24 hours and translated into English by professional English major when w riting the manuscript.Data were analyzed with content analysis.At the outset of the interviews,the purpose of the research and the patient’s rights were clearly explained in informed consent.

Results

Results from the quantitative method were shown in Table 1 and Table 2

Table 1 the evaluation of pain level before and after the treatment

Table 2 SF-MPQ score

Results from the qualitative method were shown as follows.

1)Pain alleviation.The combination of external application of Chinese medicine formula and analgesic drugs changed the patient’s pain nature from extensive to mild pain.Pain intensity had been lowered down significantly.

D1:“I feel headache,my head even cannot move an inch.The cervical also buzz.My chest,back and legs are painful as well.Aches and pains are all over the body.It’s so painful each night that I cannot fall into sleep.I just want to die sometimes.”

D6: “It’s so obvious that my head feels good,I feel clear-headed.The pain has greatly alleviated.I can even sit up on bed”

D14:“I feel great.Although there’s still tiny pain in my chest,I feel much better overall.”

2)Improvements on coping with daily life.Along with the effect on pain relief was the fact that it added more confidence to the patient in coping with daily life.Before the therapy,the patient felt hopeless and desperate with suicidal thoughts for many times.The therapy significantly changed his life.He became more energetic and positive.He can walk by himself alone and enjoyed sound sleep at night.

D1: “The pain frightens me.It’s so torturing that sometimes I just want to die.I cannot sleep,or can only sleep 2-3 hours at most…..My whole body feels weak.I don’t want to eat anything….I dare not move,even an inch.”

D6: “Though it’s still a little painful,I’m not afraid of the pain as before now.M y sleep and appetite are much better than before”

D14:“I can eat quite a lot than before,today I just eat two bowls of rice…I feel full of strength,can also carry out appropriate activities,I can eat by my own now and walk for several minutes,today I just walked for 3 minutes.Now I feel very energetic.”

Discussion

Cancer pain is generally caused by excess or deficiency.The pathogenesis of excess pain and deficiency pain are characterized as“the pain caused by stagnation”and “the pain caused by insufficient nourishment”,respectively.However,cancer pain often manifested as the coexistence of deficiency and excess in clinic[7].Chemo-radiotherapy can lead to further dual deficiency of qi and blood.The healthy qi is failing to resist pathogen,leading to the qi,blood,yin and yang of viscera damage,which mainly manifested as deficiency of yang qi[8].After multiple courses of chemo-radiotherapy,patients’healthy qi and yang qi are deficient and damaged,and the function of viscera declined.The deficiency of healthy qi,the overall damage of qi,blood,yin and yang,the cold due to yang deficiency,the phlegm due to coagulate body fluid and blood stasis cause the interaction between cancerous toxin and pathogen,such as cold,phlegm and blood stasis,congesting in meridians and collaterals,therefore giving rise to cancer pain[9].

The patient in this case has fixed hypochondriac pain on both sides ribs.Cold would make pain worse,while warm can relieve the pain.Patients prefer warm th and massage.Such manifestation is undoubtedly classified into “yin syndrome”from local pattern differentiation in Chinese medicine.Therefore,the methods of warm ing yang and dissipating cold,removing toxin and dissipating pathogenic accumulation,dredging collaterals and relieving pains are used by TCM practitioners in external treatment,which can warm and dredge meridians and collaterals,thereby resolving cold condensation,phlegm stagnation and blood stasis in local pain.In this formula,Rougui(Cinnamom i Cortex)exerts the effects of warming and dredging meridians and collaterals and dissipating cold and relieving pains.So is the Dingxiang(Caryophylli Flos).The eugenol existing in Dingxiang(Caryophylli Flos)has the effects of local anesthesia and pain relief[10].As the minister medicinal in this formula,both Quanxie(Scorpio)and Chuanshanjia(Manis Squama)can purge toxin,dissipate pathogenic accumulation,dredge the collaterals and relieve pains,so they have a direct anti-tumor effect[11-12].Xiangfu(Cyperi Rhizoma)and Zhiqiao(Aurantii Fructus)are also the minister medicinal that used for moving qi and relieving pains,while raw Banxia(Pinelliae Rhizoma)is for drying dampness,resolving phlegm and relieving swelling and pains.As the assistant medicinal,Xiebai(Allii Macrostemonis Bulbus)can help Rougui(Cinnamom i Cortex)to activate yang,dissipate pathogenic accumulation,move qi and relieve pains.And Heshouwu(Polygoni Multiflori Radix)can also help to remove toxin and dissipate pathogenic accumulation.The abovementioned formula can overall warm yang,dissipate the cold,remove toxin,dissipate pathogenic accumulation,dredge the collaterals and relieve pains.In the solvent which used for coordinating the drug actions of the formula,the liquor has the pungent flavor,which can dissipate,moisten and move qi and blood;the honey has the sweet flavor playing the role of nourishing,harmonizing and moderating qi and blood,as well as relieving pains slightly;and the ginger extract can open sweat pore and promote drug absorption.