Factors Associated with the Efficacy of Trigger Point Injection in Advanced Cancer Patients

Abstract

Background:

Few studies have reported the efficacy of trigger point injection (TPI) to myofascial trigger points (MTrPs) in advanced cancer patients. Factors that are associated with TPI efficacy have not yet been elucidated.

Objective:

The study was aimed at evaluating factors that are associated with TPI efficacy to MTrPs in advanced cancer patients.

Design:

Factors that are associated with TPI efficacy were retrospectively identified based on a comparison between clinically relevant responders and nonresponders by using multivariate regression analysis.

Setting/Subjects:

One hundred five advanced cancer patients who visited the Palliative Care Department with a chief complaint of pain and who received TPI treatment to the MTrP at the pain site.

Results:

The TPI efficacy rate on the day after TPI treatment was 0.59 (95% confidence interval [CI]: 0.50–0.68). Significant factors associated with TPI efficacy were coexistence of cancer pain with MTrP at the pain site (odds ratio [OR]: 3.87, 95% CI: 1.21–12.4), MTrP at areas other than lower back or hip (OR: 6.45, 95% CI: 1.98–21.0), and fewer MTrPs (OR: 0.64, 95% CI: 0.42–0.99). Coexistence of cancer pain at the pain site of the chief complaint was observed in 64% of study subjects (95% CI: 0.55–0.73).

Conclusions:

The TPI efficacy is likely high when advanced cancer patients have fewer MTrPs together with cancer pain at areas other than the lower back or hip. MTrPs in advanced cancer patients are more commonly observed together with cancer pain rather than independently. Healthcare providers should recognize the relationship between MTrP and cancer pain and proactively perform physical examinations to detect MTrPs for potential TPI.

Introduction

Surveys indicate that pain is experienced by more than two-thirds of advanced cancer patients.¹ Epidemiological studies generally categorize the pain as (1) directly caused by the cancer process or related phenomena (cancer pain); (2) by treatment (cancer treatment-related pain); or (3) unrelated to the cancer process.² In ∼10% of cancer patients suffering from pain, pain is unrelated to the disease or treatment and is most often caused by muscle and connective tissue disorders.³ Pain caused by myofascial trigger points (MTrPs) is not directly related to the cancer process. The criteria for MTrPs were modified, and these are now defined as hyperirritable nodules located within a taut band of skeletal muscle that when palpated is tender and produces referred pain.⁴ MTrPs are a key component of the pathophysiology of myofascial pain syndrome.⁵ The prevalence of MTrPs was reported as 30% to 93% among patients who complain of pain.^6,7

Cancer pain treatment generally involves the use of medication as a standard according to the World Health Organization guidelines. However, there are no reports demonstrating the efficacy of analgesic medication such as opioids for the treatment of MTrPs. Thus, treatment of MTrPs requires approaches that are different from those used to manage cancer pain. Treatments for MTrP in noncancer patients include trigger point injection (TPI), needling, sprays and stretching, and massages.^8,9 Of the invasive therapies, TPI is the most commonly used technique.¹⁰ The main objective of TPI is to inactivate the trigger point, thereby reducing pain and restoring function.

TPI is also employed for fast pain relief or as a diagnostic tool for determining whether the pain originates from trigger points.¹⁰ The current evidence, however, does not demonstrate that the TPI is more efficacious than placebo.^8,11 In addition, no studies have evaluated the treatment of MTrPs in advanced cancer patients.

Therefore, the evaluation of TPI efficacy has been anticipated. To optimize TPI therapy against MTrP, it is important to determine background factors that are associated with the TPI efficacy in advanced cancer patients. In advanced cancer patients, progression of overall pain and a decrease in performance status (PS) are typically observed. Most cancer patients complaining of pain have cancer pain (85%), and the pain intensity is increased with cancer progression.¹² In addition, 9% of patients have pain caused by disuse syndrome, which is characterized by extensive muscle pain and decubital pain, and the incidence is increased with cancer advancement.¹²

The efficacy of TPI against MTrP in the lower back or hip has not been evaluated even in noncancer patients.⁸ The effects of TPI have been demonstrated at the molecular level.¹³ The etiology and pathogenesis of trigger points, however, have not yet been elucidated, and the precise mechanism by which TPI inactivates the trigger points is still unknown.

This study aimed at retrospectively evaluating background factors that are associated with the efficacy of TPI in advanced cancer patients with MTrPs at the site of pain corresponding to the chief complaint and who underwent TPI.

Methods

Study subjects and subject eligibility criteria

A total of 385 stage III/IV advanced cancer patients visited the Palliative Care Department at the Kansai Medical University Hospital with a chief complaint of pain between May 2015 and October 2016. Among them, MTrP-induced pain was observed at the pain site corresponding to that of the chief complaint in 119 patients (30.9%). In this study, we selected 105 out of 117 patients who received TPI to the MTrP as study subjects after excluding 12 patients who met the exclusion criteria (Fig. 1). The exclusion criteria included (1) any changes in analgesic medication or intervention with nerve block during the period from TPI to the time point at which efficacy was evaluated on the next day (10 patients excluded), and (2) psychiatric disorder prohibiting communication (2 patients excluded).

FIG. 1.

Scheme of study subject selection. MTrP, myofascial trigger point; TPI, trigger point injection.

Study analytical parameters

In this study, we retrospectively examined medical records from each study subject. The analytical parameters included demographic factors, Eastern Cooperative Oncology Group (ECOG) PS scoring, cancer type, clinical stage, type of cancer therapy, and amount of opioids used. We extracted the following additional information: TPI efficacy rate, site of TPI, the number of TPIs, presence or absence of concurrent cancer pain together with MTrP at the pain site of the chief complaint, and presence or absence of opioid usage for the evaluation of potential factors that are associated with TPI efficacy.

The primary end point of the study was identification of factors that are associated with TPI efficacy based on the comparison between clinically relevant responders and nonresponders.

Criteria for diagnosis of MTrP

MTrP was diagnosed when the patient met all of the following four criteria: (1) tender spot in a taut band; (2) patient pain recognition on tender spot palpation; (3) predicted pain referral pattern (the pain distribution expected from a trigger point in that muscle); and (4) local twitch response (a transient local contraction of skeletal muscle fibers in response to palpation or needling). We referred to Simons' criteria, which is recommended as being essential for MTrP diagnosis.^4,6,14 MTrP has been classified as active (producing a clinical pain complaint) or latent (nonsymptom producing but tender on palpation).⁴ This study focused on only active MTrPs.

Criteria for diagnosis of cancer pain

Cancer pain is the pain that is directly caused by the cancer process, and it includes visceral pain, somatic pain, and neuropathic pain.¹⁵ In the present study, cancer pain was diagnosed when the morphological examination revealed abnormality at the pain site of the chief complaint and two independent pain treatment specialists concluded that pain attributed to the pain.

Criteria for coexistence of cancer pain with MTrP at the pain site

Clinically relevant coexistence was determined when there were tumors that themselves caused cancer pain and taut bands of MTrP at the same pain site. Pain sites were divided into right and left neck, chest, abdomen, upper back, lower back, hip, and each limb.

Criteria of TPI efficacy

Clinically relevant efficacy was determined when a reduction of pain intensity, and either complete or considerable pain relief was achieved and was reflected in the Pain Relief Scale.

Pain intensity was evaluated based on the Numerical Rating Scale (NRS). The 11-point NRS from 0 (no pain) to 10 (worst possible pain) was used to measure pain intensity based on average pain in the past 24 hours.¹⁶ The efficacy rate was determined as the rate of the patients with ≥33% improvement in NRS.¹⁷ The Pain Relief Scale reflected the patient's self-judgment on a 4-point scale, consisting of complete relief, a lot of relief, slight relief, and no change.

TPI was applied to all of the active MTrPs observed at the pain site of the chief complaint. As the TPI, 1 mL of 0.1% dibucaine was injected to each pain site with a thin needle (27G, 19 mm).

Statistical analysis

Among the study subjects, a coexistence rate of cancer pain and MTrP, and TPI efficacy rate were calculated. All data were reported as means with 95% confidence interval (CI), ranges, or frequencies (%), as appropriate. We used Wilcoxon signed-rank test for the dependent variables, including age, sex, PS, MTrP site, number of MTrPs, presence or absence of coexistence of cancer pain with MTrP, and presence or absence of opioid use. In addition, multivariable logistic regression analysis was performed with a dependent variable of TPI efficacy and seven independent variables, including age, sex, PS, MTrP site, number of MTrPs, presence or absence of coexistence of cancer pain with MTrP, and presence or absence of opioid use.

A p-value less than 0.05 was regarded as statistically significant. Statistical procedures were conducted by using SPSS version 18.0J for Macintosh (SPSS, Inc. IBM, Chicago, IL).

Results

Table 1 shows demographic and clinical characteristics of the study subjects. Coexistence of cancer pain together with MTrP at the pain site of the chief complaint was observed in 67 study subjects (64%, 95% CI: 0.55–0.73). No coexistence of MTrP and cancer treatment-related pain was observed at the pain site of the chief complaint.

Table 1.

Demographic and Clinical Characteristics of Study Subjects

	n	%		n	%		n	%
Patient type			Primary cancer site			Dose of opioids^a, mg/day
Outpatient	46	43.8	Lung	14	13.3	None	38	36.2
Inpatient	59	56.2	Gastrointestinal	32	30.5	<30	17	16.2
Sex			Liver, pancreas, biliary system	16	15.3	30–59	18	17.1
Male	48	45.7	Breast	14	13.3	60–89	11	10.5
Female	57	54.3	Gynecological	9	8.6	90–119	5	4.8
Age, years			Urological	8	7.6	≤120
<50	13	12.4	Head and neck	4	3.8	Coexistence of cancer pain with MTrP^b
50–59	16	15.2	Others	8	7.6	Yes	67	63.8
60–69	32	30.5	Cancer stage at diagnosis			No	37	36.2
70–79	34	32.4	III	4	3.8	Coexistence of cancer treatment-related pain with MTrP^c
≤80	10	9.5	IV	101	96.2	Yes	0	0
PS			Medical treatments			No	7	100
0	8	7.6	Chemotherapy	44	41.9
1	31	29.5	BSC	61	58.1
2	25	23.8
3	20	19.1
4	21	20

Dose of opioids is expressed as oral dose level of morphine (mg/dl). For conversion: parenteral morphine: oral morphine = 1:2, parenteral oxycodone: oral morphine = 1:2, oral oxycodone: oral morphine = 2:3, fentanyl: morphine = 1:100, oral methadone: oral morphine = 1:8.

Total 105 subjects with MTrP are further classified by coexistence of cancer pain.

Total 105 subjects with MTrP are further classified by coexistence of cancer treatment-related pain.

BSC, best supportive care; ECOG, Eastern Cooperative Oncology Group; MTrP, myofascial trigger point; PS, ECOG performance status.

The TPI efficacy rate on the day after TPI treatment was 0.59 (95% CI: 0.50–0.68). No adverse events occurred during any of the TPIs performed throughout the evaluation period. Based on the criteria of clinically relevant efficacy, the study subjects were classified into 62 responders and 43 nonresponders. The responders demonstrated significantly better PS compared with the nonresponders (p < 0.001) (Table 2). Clinically relevant responders demonstrated higher incidence of MTrPs in areas such as the neck and upper back rather than the lower back and hip (p < 0.001), smaller number of MTrPs (p < 0.001), and higher coexistence rate with cancer pain at the pain site of the chief complaint (p < 0.001) (Table 2).

Table 2.

Comparison in Clinical Characteristics of MTrP between Responders and Nonresponders

	Responders (n = 62)		Nonresponders (n = 43)
	Mean	SD	Mean	SD	p
	64.5	12.4	65.7	12.4	0.648
Aging (years old)	n	%	n	%
Sex
Male	26	41.9	22	51.2	0.662
Female	36	58.1	21	48.8

	Mean	SD	Mean	SD
	1.73	1.09	2.74	1.26	<0.001
PS	n	%	n	%
0	6	9.7	2	4.6
1	24	38.7	7	16.3
2	18	29	7	16.3
3	9	14.5	11	25.6
4	5	8.1	16	37.2

MTrP Site	n	%	n	%
Lower back or hip	7	11.3	27	62.8	<0.001
Lower back	6		23
Hip	1		9
Other than lower back or hip	55	88.7	16	37.2
Neck	25		9
Upper back	18		7
Chest	4		0
Abdomen	6		0
Limb	2		0

	Mean	SD	Mean	SD
	1.84	0.93	3.4	1.98	<0.001
Number of MTrP	n	%	n	%
Number
1–2	50	80.7	19	44.2
3–4	11	17.7	11	25.6
5–?	1	1.6	13	30.2

Coexistence of cancer pain	n	%	n	%
Yes	51	82.3	16	37.2	<0.001
No	11	17.7	27	62.8

Dose of opioids ^a , mg/day	n	%	n	%
None	19	30.6	19	44.2	0.179
Use	43	69.4	24	55.8
<30	11		6
30–59	9		9
60–89	9		2
90–119	3		1
120≦	10		6

Dose of opioids is expressed as oral dose level of morphine (mg/day). For conversion: parenteral morphine: oral morphine = 1:2, parenteral oxycodone: oral morphine = 1:2, oral o xycodone: oral morphine = 2:3, fentanyl: morphine = 1:100, oral methadone: oral morphine = 1:8.

SD, standard deviation.

Multivariable logistic regression analysis determined three relevant factors associated with TPI efficacy, which were MTrP at pain sites in areas other than the lower back or hip (odds ratio [OR]: 6.45, 95% CI: 1.98–21.0), number of MTrPs (OR: 0.64, 95% CI: 0.42–0.99), and coexistence of cancer pain with MTrP (OR: 3.87, 95% CI: 1.21–12.4) (Table 3).

Table 3.

Relative Factors that Influenced Efficacy of Trigger Point Injection

Variable	Coefficient β	SD	Wald	p	OR	95% CI
Age	0.015	0.021	0.497	0.481	1.015	0.97–1.06
Sex, female	0.352	0.521	0.457	0.499	1.422	0.51–3.95
PS	−0.133	0.237	0.316	0.574	0.875	0.55–1.39
MTrP site, other than lower back or hip	1.863	0.603	9.565	0.002	6.446	1.98–21.0
Number of MTrPs	−0.44	0.219	4.014	0.045	0.644	0.42–0.99
Coexistence of cancer pain	1.354	0.594	5.195	0.023	3.874	1.21–12.4
Opioid use	−0.544	0.58	0.879	0.348	0.58	0.19–1.81

CI, confidence interval; OR, odds ratio; SD, standard error.

Discussion

To the best of our knowledge, this study is the first to report the background factors that are associated with TPI efficacy against MTrP in patients with advanced cancer.

The first critical point in this study was that the coexistence of cancer pain and MTrP is a significant relative factor contributing to better TPI efficacy. This result suggests that when MTrP and cancer pain coexist, TPI against the MTrP should be applied aggressively. Moreover, TPI efficacy increases when MTrP is the main contributor to overall pain. Conversely, when there is less contribution of the MTrP to the overall pain, nerve block therapy could be considered an obstacle against effective pain control.¹⁸ Given the other relative factors (MTrP site and number of MTrPs), the following hypothesis can be considered. A larger number of the responders had cancer pain, which could cause continuous muscle tension in the surrounding muscles owing to flight response. This, consequently, resulted in the development of an MTrP. The responders had better PS, meaning that they likely required less bed rest, and thus, there was less irritation to body support points compared with nonresponders. As a result, fewer MTrPs could have developed in areas other than the lower back or hip. In this study, cancer pain could be ameliorated with analgesic medication at the subject's request selection; subsequently, MTrP-induced pain became more predominant.

The pathogenesis of MTrP has not been fully elucidated; however, flight response from pain, limited body posture, and continuous muscle tension caused by remaining in the same position for long periods of time are considered contributing factors.¹⁹ According to the polymodal theory, the causes of MTrP formation in this pattern were inflammatory edema and persistent myotonia secondary to a withdrawal reflex associated with cancer pain. A withdrawal reflex is a flexion reflex that evokes defensive responses to noxious stimuli and allows the occurrence of a contraction of the flexors ipsilateral to the stimuli and a relaxation of the extensors.²⁰ One such example includes abdominal wall pain. The abdominal wall pain observed commonly in myofascial pain syndrome has been previously reported to occur in 11% of patients with abdominal pain of an obscure origin.²¹ A withdrawal reflex is considered one of the causes of MTrP formation.²¹ Conversely, nonresponders had poorer PS requiring prolonged bed rest, subsequently resulting in multiple points of muscle tension to support the body, especially in the lower back and hip compared with the responders. MTrP-induced pain in the nonresponders was likely accompanied with pain secondary to the disuse syndrome, resulting in low contribution of MTrP-induced pain to overall pain. It was reported that 9% of cancer patients complaining of pain had disuse syndrome-related pains such as extensive muscle pain and decubital pain, which are refractory to pain relief with analgesic medication.¹²

Another critical point of this study was that MTrPs in advanced cancer patients were more commonly observed together with cancer pain rather than independently. Although the relationship between MTrP and postoperative pain syndrome, which is categorized into cancer treatment-related pain, has been reported,^22,23 no reports have indicated a relationship between MTrP and cancer pain in advanced cancer patients. Since MTrP is accompanied with multiple pains and pain behaviors, it is often overlooked.²⁴ When multiple types of pains coexist in advanced cancer patients, only cancer pain tends to be diagnosed as a representative pain.

In this study, MTrP was observed in 30.9% of advanced cancer patients complaining of pain; however, MTrP has not been well recognized in clinical practice. In a case series, it was reported that increased opioid doses against MTrPs coexisting with cancer pain resulted in delirium.²⁵ In this article, a physical examination of the pain site corresponding to that of the chief complaint was not performed because of cancer pain, overlooking MTrPs.

Diagnosis of MTrP requires a careful physical examination. A previous paper suggested the clinical significance of physical examinations in advanced cancer patients, among whom 83% of the patients showed a positive reaction to the examinations objectively as well as subjectively.²⁶ Healthcare providers should recognize the relationship between MTrP and cancer pain and proactively perform physical examinations at the pain site.

This study has several limitations. First, the study subjects were patients with intractable pain who visited our palliative care center with a chief complaint of pain; therefore, there was a subject population-related bias. In our hospital, almost all patients with intractable pain visit our center. We recognize that advanced cancer patients who do not visit our center have low pain intensity and MTrP frequency. Second, both data extraction and analysis were performed by a single primary investigator (the primary author) without blinded analysis. Third, only acute efficacy on the day after the TPI treatment was evaluated; therefore, no long-term effect was assessed. Lastly, the study was conducted at a single facility with lack of versatility, warranting a large scale of data confirmation. Based on these limitations, the results of this study should be considered preliminary.

Conclusions

Footnotes

Acknowledgments

The authors would like to thank Assistant Professor Hiroto Isiki (Department of Palliative Oncology Research Hospital, the Institute of Medical Science, The University of Tokyo) for advice on the experimental design of this article.

Author Disclosure Statement

No competing financial interests exist.

References

Goudas

, Bloch

, Gialeli-Goudas

, et al.: The epidemiology of cancer pain. Cancer Invest, 2005; 23:182–190.

Portenoy

: Cancer pain. Epidemiology and syndromes. Cancer, 1989; 63:2298–2307.

Marcus

: Pain in cancer patients unrelated to the cancer or treatment. Cancer Invest, 2005; 23:84–93.

Tough

, White

, Richards

, et al.: Variability of criteria used to diagnose myofascial trigger point pain syndrome—Evidence from a review of the literature. Clin J Pain, 2007; 23:278–286.

Hong

: Pathophysiology of myofascial trigger point. J Formos Med Assoc, 1996; 95:93–103.

Simons

: Clinical and etiological update of myofascial pain from trigger points. J Musculoskelet Pain, 1996; 4:93–122.

Skootsky

, Jaeger

, Oye

: Prevalence of myofascial pain in general internal medicine practice. West J Med, 1989; 151:157–160.

Scott

, Guo

, Barton

, et al.: Trigger point injections for chronic non-malignant musculoskeletal pain: A systematic review. Pain Med, 2009; 10:54–69.

Edwards

, Knowles

: Superficial dry needling and active stretching in the treatment of myofascial pain–a randomized controlled trial. Acupunct Med, 2003; 21:80–86.

10.

Criscuolo

: Interventional approaches to the management of myofascial pain syndrome. Curr Pain Headache Rep, 2001; 5:407–411.

11.

Cummings

, White

: Needling therapies in the management of myofascial trigger point: A systematic review. Arch Phys Med Rehabil, 2001; 82:986–992.

12.

Grond

, Zech

, Diefenbach

, et al.: Assessment of cancer pain: A prospective evaluation in 2266 cancer patients referred to a pain service. Pain, 1996; 64:107–114.

13.

Shah

, Phillips

, Danoff

, et al.: An in vivo microanalytical technique for measuring the local biochemical milieu of human skeletal muscle. J Appl Physiol, 2005; 99:1977–1984.

14.

Simons

: Muscular pain syndromes. In: Friction

, Award

(eds): Myofascial Pain and Fibromyalgia. New York: Raven Press, 1990, pp. 1–41, 114.

15.

Swarm

, Abernethy

, Anghelescu

, et al.; National Comprehensive Cancer Network: Adult cancer pain. J Natl Compr Canc Netw, 2010; 8:1046–1086.

16.

Caraceni

, Cherny

, Fainsinger

, et al.: Pain measurement tools and methods in clinical research in palliative care: Recommendations of an expert working group of the European association of palliative care. J Pain Symptom Manage, 2002; 23:239–255.

17.

Farrar

, Portenoy

, Berlin

, et al.: Defining the clinically important difference in pain outcome measures. Pain, 2000; 88:287–294.

18.

Swarm

, Karanikolas

, Cousins

: Injection, neural blockade, and implant therapies for pain control. In: Hanks

, Cherny

, Christakis

, et al., (eds): Oxford Textbook of Palliative Medicine, 4th ed. New York: Oxford University Press, 2009, pp. 734–755.

19.

Saxena

, Chansoria

, Tomar

, et al.: Myofascial pain syndrome: An overview. J Pain Palliat Care Pharmacother, 2015; 29:16–21.

20.

Schouenborg

, Kalliomäki

: Functional organization of the nociceptive withdrawal reflexes. I. Activation of hindlimb muscles in the rat. Exp Brain Res, 1990; 83:67–78.

21.

Nazareno

, Ponich

, Gregor

: Long-term follow-up of trigger point injections for abdominal wall pain. Can J Gastroenterol, 2005; 19:561–565.

22.

Torres Lacomba

, Mayoral del Moral

, Coperias Zazo

, et al.: Incidence of myofascial pain syndrome in breast cancer surgery: A prospective study. Clin J Pain, 2010; 26:320–325.

23.

Cardoso

, Rizzo

, de Oliveira

, et al.: Myofascial pain syndrome after head and neck cancer treatment: Prevalence, risk factors, and influence on quality of life. Head Neck, 2015; 37:1733–1737.

24.

Fricton

, Steenks

: Diagnosis and treatment of myofascial pain. Ned Tijdschr Tandheelkd, 1996; 103:249–253.

25.

Hasuo

, Ishihara

, Kanbara

, et al.: Myofascial trigger points in advanced cancer patients. Indian J Palliat Care, 2016; 22:80–84.

26.

Kadakia

, Hui

, Chisholm

, et al.: Cancer patients' perceptions regarding the value of the physical examination: A survey study. Cancer, 2014; 120:2215–2221.