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BJPT 191 1---11 ARTICLE IN PRESS

1 Brazilian Journal of Physical Therapy 2018;xxx(xx):xxx---xxx
2

3 Brazilian Journal of
Physical Therapy
https://www.journals.elsevier.com/brazilian-journal-of-physical-therapy

MASTERCLASS

4 Explaining pain following cancer: a practical guide for

5 clinicians
6 Q1 Jo Nijs a,b,∗ , Amarins J. Wijma a,e , Laurence Leysen a , Roselien Pas a ,
7 Ward Willaert a , Wouter Hoelen c,d , Kelly Ickmans a,b , C. Paul van Wilgen a,e

a
8 Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education & Physiotherapy, Vrije Universiteit
9 Brussel, Brussels, Belgium
b
10 Chronic Pain Rehabilitation, Department of Physical Medicine and Physiotherapy, University Hospital Brussels, Brussels, Belgium
c
11 De Berekuyl, Private Practice for Physiotherapy in Oncology & Lymphology, Hierden, The Netherlands
d
12 The Berekuyl Academy, Hierden, The Netherlands
e
13 Transcare Transdisciplinary Pain Management Center, Groningen, The Netherlands

14 Received 15 October 2018; received in revised form 4 December 2018; accepted 10 December 2018

15 KEYWORDS Abstract
Q2
16 Oncology; Background: Pain is one of the most prevalent and debilitating symptom following cancer
17 Education; treatment.
18 Communication; Objectives: This paper entails a practical guide for clinicians willing to apply pain neuroscience
19 Rehabilitation; education (PNE) in this specific population, or clinical researchers willing to examine the effects
20 Breast cancer; of PNE in patients suffering from pain following cancer.
21 Prostate cancer Results: Patient-specific information (i.e. beliefs, cognitions, pain memories, social factors) as
22 well as identification of the dominant pain mechanism are needed to tailor the education to
23 the specific needs and beliefs of the patient. Therapists require an in-depth understanding
24 of pain mechanisms, the skills to explain to their patients various pain mechanisms, spe-
25 cific communication skills (e.g. Socratic-style dialogof education) and experience with current
26 evidence-based biopsychosocially-driven pain management strategies for successful implemen-
27 tation of PNE in the clinic. Rather than purely focusing on the biomedical characteristics of
28 pain following cancer (e.g., tissue damage due to past cancer treatment), PNE implies teaching
29 patients about the underlying biopsychosocial mechanisms of pain. Its application is backed-up
30 by mounting evidence supporting the effectiveness of PNE in non-cancer pain populations, and
31 a pilot study in patients having pain following cancer.
32 Conclusion: PNE is a potential solution to improve pain outcome in cancer survivors. Fur-
33 ther research using sufficiently powered and well-designed randomized clinical trials should
34 be conducted to examine the potential of PNE in patients having pain following cancer.
35 © 2018 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Published by Elsevier
36 Editora Ltda. All rights reserved.

37 ∗ Corresponding author at: Vrije Universiteit Brussel, Building F-KIMA, Laarbeeklaan 103, BE-1090 Brussels, Belgium.
E-mail: Jo.Nijs@vub.be (J. Nijs).

https://doi.org/10.1016/j.bjpt.2018.12.003
1413-3555/© 2018 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Published by Elsevier Editora Ltda. All rights reserved.

Please cite this article in press as: Nijs J, et al. Explaining pain following cancer: a practical guide for clinicians. Braz
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38 Background suffering from pain following cancer. This paper entails a 98

practical guide for clinicians willing to apply PNE in this spe- 99

cific population, or clinical researchers willing to examine 100

39 Q3 Life expectancy for people following cancer treatment the effects of PNE in patients suffering from pain following 101
40 has increased due to the early detection and advances in cancer. 102
41 cancer treatment.1,2 Unfortunately, cancer survivors often
42 face long-term symptoms that arise or persist beyond
43 the completion of treatment, making it an increasingly Information needed to allow 103
44 important population for the field of physical therapy and individually-tailored pain neuroscience 104
45 rehabilitation. Together with fatigue, pain is the most fre-
education 105
46 quent persistent symptom following cancer and cancer
47 treatment,3 accounting for poor quality of life and day-
48 to-day functioning.4---8 The high prevalence of pain in the In order to allow the clinician to adopt the PNE to the spe- 106

49 growing cancer survivor population is of considerable con- cific features, needs and perceptions of patients suffering 107

50 cern due to the fact that pain is associated with reduced from pain following cancer, a thorough assessment within a 108

51 quality of life and day-to-day functioning.4---8 biopsychosocial framework is needed. This includes, but is 109

52 In the treatment phase of cancer, pain may be consid- certainly not limited to, the items listed in Table 1. A com- 110

53 ered to be part of the suffering, but after this process it is prehensive overview of all variables required to obtain a 111

54 difficult for patients to understand that they are ‘cured’ or comprehensive biopsychosocial profile of the patients having 112

55 in remission yet continue to suffer from pain. Most patients pain following cancer is beyond the scope of this paper. 113

56 experience dull pain and fail to identify its origin; which

57 tends to be frightening and cause worrisome when one has Beliefs, cognitions and pain memories 114
58 had cancer. The happiness of having survived and success-
59 fully ‘beaten’ cancer, however with a toll: he/she now has
During history taking, pain perceptions (e.g. ‘‘You have suc- 115
60 to deal with persistent and debilitating pain every single
cessfully beaten cancer, yet you continue to suffer from 116
61 day. In general, cancer patients indicate that they do not
pain. What do you think is causing your pain?’’) and cogni- 117
62 have enough knowledge regarding pain during or after can-
tions (e.g. pain catastrophizing assessed through the Pain 118
63 cer, what the possibilities of pain relief are and how they
Catastrophizing Scale24,25 ) of the patient should be thor- 119
64 can access support when needed.9,10 Hence, the education
oughly assessed. Most important are perceptions about the 120
65 of patients about pain should be the first part of the mana-
physical and mental causes of pain as well as the conse- 121
66 gement of pain following cancer.
quences (Table 1). Furthermore, the following factors should 122
67 A meta-analysis of 21 trials concluded that patient-based
be questioned; the expectations for care (anticipated out- 123
68 educational interventions are effective for improving pain
come as well as the content of the treatment), expectations 124
69 severity, knowledge and self-efficacy for treating cancer
regarding the prognosis of their pain problem, coherence 125
70 related pain.11 Yet education about pain is underused in
(the extent to which one understands the pain) and emo- 126
71 the field of oncology.11 The content of the used educa-
tional representation of the pain.26 127
72 tion is variable and poorly established,11 with most of the
In some patients, pain is one of the reasons why they 128
73 educational interventions for cancer patients restricted to
initially consult a physician. In such instances, pain will be 129
74 more biomedical pain management instructions (e.g., use
strongly linked to the cancer itself, will be connected in the 130
75 of analgesics).11 The latter is problematic as the biomedi-
brain with receiving the cancer diagnosis, and hence may 131
76 cal model falls short in explaining (persistent) pain following
become an uncertain threat of disease recurrence.27 Indeed, 132
77 cancer, therefore current patient-based educational inter-
receiving the cancer diagnosis is a very stressful event,28 133
78 ventions emphasize a biopsychosocial framework.12 When
leading to the release of cortisol and adrenaline which facil- 134
79 providing a pain education program to patients suffering
itate long-term potentiation of excitatory synapses within 135
80 from cancer related pain, implementation of contemporary
parts of the central nervous system.29 The mechanism 136
81 pain neuroscience into this program seems warranted.13 This
of long-term potentiation is crucial for (re)learning and 137
82 includes explaining to patients that the pain is the sum of
developing new (pain-related) memories,30,31 and hence for 138
83 many processes within the nervous system, which may or
altering pain memories in the brain.32 Stress burns those 139
84 may not include nociception, and thus frequently poorly
memories (connections) in the brain, and they will not go 140
85 reflects current tissue damage or illness status. In non-
away easily and therefore can be a source of chronic pain fol- 141
86 cancer pain populations, such pain neuroscience education
lowing cancer. In addition to these stress mechanisms, other 142
87 (PNE) is welcomed very positively,14,15 and has proven to be
factors such as fear and memory, fear of pain and diagno- 143
88 effective in changing pain beliefs and improving health sta-
sis, neuroinflammation, the influence of drugs on the brain, 144
89 tus as well as pain coping strategies.14---22 An observational,
depression and anxiety may contribute to such pain memo- 145
90 uncontrolled study showed decreased pain, catastrophizing
ries. It is of importance to question whether such (or other) 146
91 (including pain helplessness and rumination about pain) and
pain memories are relevant to the patient (e.g. ‘‘Was pain 147
92 improved pain related quality of life (medium effect sizes)
one of the reasons why you consulted a physician and how 148
93 following a single session of PNE in 30 patients suffering from
you found out you had cancer?’’), as they can be addressed 149
94 pain following cancer.23
(i.e. explained) during pain neuroscience education. 150
95 This article will introduce PNE in the field of oncology,
Maladaptive cognitive patterns, such as catastrophizing, 151
96 specifically applied to patients suffering from pain following
perceived injustice or perceived harm are equally impor- 152
97 cancer. It is explained how PNE can be applied in patients
tant to recognize (Table 1 provides the mode assessment 153

Please cite this article in press as: Nijs J, et al. Explaining pain following cancer: a practical guide for clinicians. Braz
BJPT 191 J
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Phys Ther. 2018, https://doi.org/10.1016/j.bjpt.2018.12.003
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Explaining pain after cancer 3

Table 1 Potential items of importance to question/assess before initiating pain neuroscience education for pain following
cancer (and information needed to individually tailor the education).

Item Mode of assessment

Past cancer & pain treatment Questioning + medical record screening
Current cancer & pain treatment Questioning + medical record screening
Premorbid pain Questioning + medical record screening
Pain evolution Questioning
Pain location Pain drawing88,89
Pain history, including possible pain memories Questioning + medical record screening
Scar tissues Clinical examination including inspection, palpation
and possible movement investigation
Musculoskeletal system Clinical examination including inspection, palpation
and possible movement investigation
Pain beliefs/perceptions: Questioning and/or (brief) Illness Perceptions
--- Interpretation of pain by the patient Questionnaire90---92
--- Personal beliefs about provoking factors
--- Personal beliefs about etiology of pain
--- Beliefs about how long the pain will
last/anticipated course
--- Beliefs about the consequences of the pain on life
--- Beliefs about the extent of which the patient thinks
he can control the (course of the) pain
--- The extent to which one understands the pain
--- Influence of the pain on once mood
Pain coping strategy Questioning and/or a pain coping questionnaire (e.g.
Pain-Coping Inventory,93 the Vanderbilt Pain
Management Inventory94 )
Pain catastrophizing Pain Catastrophizing Scale24,25
Pain-related fear Fear of pain questionnaire95
Pain-related fear of movement Tampa Scale Kinesiophobia96
Avoidance of pain and cognitive fusion with pain Psychology Inflexibility in Pain Scale97
Anxiety State and Trait Anxiety Inventory98
Depression Beck Depression Inventory99 or Hospital Anxiety and
Depression Scale100

Pain acceptance, i.e. the extent to which they accept History taking or chronic pain acceptance
their pain questionnaire101
Pain (hyper)vigilance Pain vigilance and awareness questionnaire102
Perceived injustice Injustice experience questionnaire37
Social support Questioning

154 of each of these constructs). Pain catastrophizing com- itself, but especially the post-cancer pain as highly unfair, 171

155 prises of rumination, magnification and helplessness, and generating negative emotions that contribute to the pain 172

156 has been identified as an important treatment mediator of experience. 173

157 mindfulness-based cognitive therapy on pain intensity in Determining motivation and readiness to change is vital 174

158 women treated for primary breast cancer.33 Women with for further treatment. The perceptions about the cause of 175

159 persistent pain following breast cancer surgery can show pain and the treatment expectations are crucial to know in 176

160 high levels of pain catastrophizing that mediate alterations order to target and modify them during the treatment,38 177

161 in central pain modulatory systems.34 Indeed, when compar- which can be done using PNE. 178

162 ing post-mastectomy patients with and without post-surgical

163 pain, they did not differ in treatment or disease-related
164 variables, but differed in terms of psychological factors Social factors 179
165 (more anxiety, catastrophizing, depression and somatiza-
166 tion in the patients having pain).35 Perceived injustice or Social factors should also be assessed (through question- 180
167 perceived harm is less-well studied in the post-cancer pain ing/history taking) and can be divided into housing, social 181
168 population, but is an established prognostic factor in the environment, work, relationship with the partner (includ- 182
169 non-cancer pain population.36,37 Anecdotally, patients who ing being able to be sexually active and have an intimate 183
170 have lived a healthy life might perceive not only the cancer relationship), prior/other treatments, socioeconomic and 184

Please cite this article in press as: Nijs J, et al. Explaining pain following cancer: a practical guide for clinicians. Braz
BJPT 191 J
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Phys Ther. 2018, https://doi.org/10.1016/j.bjpt.2018.12.003
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Explain source of nociception +

Nociceptive role of the brain (dynamic pain
connectome)

Explain pain neuroscience

Neuropathic underlying neuropathic pain
mechanisms
Pain
following
cancer Central Explain pain neuroscience
underlying central sensitization
sensitization
pain

Explain pain neuroscience

Mixed pain underlying relevant pain
mechanisms

Figure 1 Pain neuroscience education for patients having pain following cancer: tailoring based on mechanism-based pain clas-
sification.

185 environmental influences (especially in low-income coun- To differentiate between the various pain mechanisms 223

186 tries, where access to hospitals and treatment can be among pain patients following cancer, identification of red 224

187 an issue). It is important to find out whether certain flags and excluding the possibility of cancer recurrence or 225

188 social factors are helpful and supportive, stressful or any other serious pathology is often the first step.41,42 Next, 226

189 unconsciously unhelpful. Other important social factors are neuropathic pain, defined as pain caused by a primary lesion 227

190 prior/simultaneous treatments and attitudes of the health- or disease of the somatosensory nervous system,43 can be 228

191 care professionals that delivered these treatments. These diagnosed by applying international guidelines.44,45 Within 229

192 prior/simultaneous treatments, advices and explanations the cancer survivor population, neuropathic pain is most 230

193 will influence the perceptions and current coping strategy prevalent, but mixed type of pain is also common, reflect- 231

194 of patients having pain following cancer. It is important to ing the complexity of the pain experience in those who 232

195 know them and to discuss them with the patient during PNE, completed cancer treatment.46 Examples of neuropathic 233

196 also to prevent contrasting views from various health care pain following cancer include neuropathy from direct insult 234

197 practitioners. during surgery and lymph node dissection, e.g. the inter- 235

198 Low social support contributes to symptoms and poor costobrachial nerve during axillary lymph node dissection47 236

199 quality of life following cancer,39,40 but tends to be an or postsurgical adhesions and inflammation in the area of 237

200 underestimated factor in clinical practice. PNE provides the the nerve.48 In case of neuropathic pain, PNE should include 238

201 opportunity to facilitate social support in patients following the underlying (sensitizing) mechanisms explaining pain and 239

202 cancer. By simply stimulating to share the PNE content with a other symptoms (e.g. sensory hypersensitivity) typically 240

203 significant other (partner, parent, child, close friend), social seen in neuropathic pain (Fig. 1). The PNE should also aim 241

204 support can be enhanced. Involvement is possible through at decatastrophizing about the ‘neuropathic pain’ diagnosis, 242

205 various ways, depending on the patient preferences (shared which can sound frightening to patients. 243

206 decision-making): inviting the significant other to join the For clinical purposes, the term nociceptive pain can be 244

207 patient to a face-to-face session of pain neuroscience edu- used when pain is proportional to nociceptive input, while 245

208 cation, the patient asking the significant other to read the central sensitization is a common pathophysiological mecha- 246

209 information leaflet or to watch an online education video nism to explain related symptoms (including pain) for which 247

210 about explaining pain. no specific organic cause can be found. Pain in patients 248

where central nervous system sensitization dominates the 249

clinical picture is labeled now as ‘nociplastic pain’ by the 250

International Association for the Study of Pain,49 who defines 251

211 Predominant pain mechanism(s) nociplastic pain as pain that arises from altered nocicep- 252

tion despite no clear evidence of actual or threatened tissue 253

212 In order to allow tailoring PNE to the underlying pain mech- damage causing the activation of peripheral nociceptors or 254

213 anisms it is important to differentiate between the 3 major evidence for disease or lesion of the somatosensory system 255

214 pain types (nociceptive, neuropathic and central sensitiza- causing the pain. In order to diagnose central sensitization 256

215 tion pain). Without such pain mechanism-based tailoring, pain, the first and either the second or third (or both) of the 257

216 PNE may include in part explanations that do not match the following three questions should be answered positively46 : 258

217 patient’s clinical picture and personal pain experience. For

218 example, explaining the mechanism of central sensitization 1. Is the pain severity disproportionate to the nature and 259

219 to someone without spreading of the pain or hypersensitivity extent of the injury or pathology (i.e., tissue damage 260

220 symptoms, might lead to confusion rather than recognizing or structural impairments which might cause nociceptive 261

221 their pain experience in the provided information, which in pain following cancer)? Frequent sources of nociception 262

222 turn might jeopardize the therapeutic alliance. following cancer include bone fractures, connective tis- 263

Please cite this article in press as: Nijs J, et al. Explaining pain following cancer: a practical guide for clinicians. Braz
BJPT 191 J
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Phys Ther. 2018, https://doi.org/10.1016/j.bjpt.2018.12.003
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Explaining pain after cancer 5

264 sue fibrosis, lymphatic cording, skin rashes, ulcers and therefore, has potentially a higher threat value compared 321

265 scars, and inflammation.46 to other (chronic) pain populations. Secondly, in this pop- 322

266 2. Does the pain pattern presents a neuroanatomical distri- ulation, fear for recurrence might be present,66 making it 323

267 bution, i.e. one that is neuroanatomically plausible for harder to reconceptualise the pain as an unreliable and 324

268 the presumed source(s) of nociception? harmless signal. Therefore, it is very important for both 325

269 3. Does the patient scores 26 or higher on part A of the Cen- patient and therapist to be confident/reassured about that 326

270 tral Sensitization Inventory?50 The Central Sensitization issue. Finally, it is possible that cancer survivors are less 327

271 Inventory assesses symptoms common to central sensiti- admissive about their pain, due to the enormous psycholog- 328

272 zation, with the total score ranging from 0 to 100.51,52 ical burden caused by the disease. 329

273 The clinimetric properties of the Central Sensitization

274 Inventory in the cancer survivor population have been
Learning objectives 330
275 examined and were found satisfactory, and the receiver
276 operating characteristic curve (ROC) analysis yielded a
The learning objectives of PNE comprise decreasing the 331
277 cutoff point of the Central Sensitization Inventory score
threat value of pain, increasing the patients’ knowledge 332
278 of 26 out of 100.53
of pain, and reconceptualising pain. In order to achieve 333

this, the patient needs to understand that all pain is pro- 334
279 In case of predominant central sensitization pain, the duced, constructed and modulated by the brain (e.g. pain 335
280 PNE content should focus on explaining the mechanisms triggered or worsened by pain anticipation, similar to antic- 336
281 of central sensitization (Fig. 1), including the increased ipatory nausea and vomiting), that their pain symptoms 337
282 sensitivity of the dorsal horn neurons, poor functioning of can partly relate to hypersensitivity of the central ner- 338
283 top-down inhibitory control and overactivity in the dynamic vous system rather and not only (ongoing) tissue damage. 339
284 pain connectome.54 Still, it is equally important to acknowledge the tissue dam- 340

age that contributes to the pain experience, but at the 341

285 Pain neuroscience education: content and same time broaden the patient’s view and understanding 342

286 protocol when applied to post-cancer pain regarding their pain. Finally, systematic evaluation of the 343

effects of exercise on a multitude of cancer-related con- 344

cerns, e.g., fatigue, sleep and mood reveals it is effective 345

287 Therapists’ prerequisites
for these impairments, but also shows some efficacy for 346

decreasing pain in this population.67 Pain beliefs such as pain 347

288 The therapist can be a psychotherapist, physical therapist,
catastrophizing,33,68 fear of movement69 and fear of can- 348
289 nurse or any other healthcare professional as long as they
cer (recurrence) can prevent patients following cancer of 349
290 have certain prerequisites for providing PNE to patients
returning to normal physical activity levels or limit effect 350
291 having pain following cancer. First, therapists require an
sizes of exercise interventions. Therefore, at the end of the 351
292 in-depth understanding of pain mechanisms55 and the dys-
PNE, the patient should be able to put their post-cancer pain 352
293 functional central nociceptive processing in those with
into the right perspective and feel less threatened by the 353
294 chronic pain.56,57 This includes a thorough understanding
pain, leading to the willingness to perform physical activity 354
295 of biopsychosocial factors in the development and sus-
with progression toward feared or avoided movements. 355
296 tainment of chronic pain.58 Second, therapists require the
297 skills to explain to their patients various pain mechanisms,
298 including central sensitization and neuropathic pain as Format 356

299 evidence-based explanations for pain following cancer.59,60

300 Third, specific communication skills are required. For ins- The format can vary from online learning to group sessions, 357

301 tance, a Socratic-style dialog of education61 is preferred one-on-one sessions to blended learning formats, but in 358

302 over ‘lecturing’ to the patient, and therapists are advised other conditions online interventions only show little pos- 359

303 to use shared decision making to optimize the therapeu- itive effects.70 Preferentially (at least part of) the PNE is 360

304 tic alliance. Finally, PNE is not a standard intervention provided individually, allowing to adopt the PNE (content) 361

305 or standalone treatment, but rather a treatment concept to the individual perceptions/beliefs. For example, patients 362

306 that should be individually tailored to the specific fea- can participate in three interactive and individual sessions 363

307 tures, needs and perceptions of patients suffering from of PNE that will last about 30 min each, or the PNE can com- 364

308 pain following cancer. Indeed, PNE typically clears the path prise of one group session (of approximately 5---6 patients 365

309 for more active approaches to pain management, ther- per group) followed by an online session and one individ- 366

310 apists should preferentially be familiar (or experienced) ual session.71 Given the social context of pain, at least one 367

311 with current evidence-based biopsychosocially-driven pain significant other is encouraged to participate. 368

312 management strategies including graded activity,62 graded To facilitate (deep) learning, the information should 369

313 exposure in vivo,63 stress-management and acceptance- be presented verbally (explanation by the therapist) and 370

314 based interventions (e.g. acceptance and commitment visually (summaries, pictures, metaphors and diagrams on 371

315 therapy).64,65 computer, whiteboard and/or paper). To assess the degree 372

316 Clinicians are advised to take into account that pain fol- of learning and to identify possible learning gaps, patients 373

317 lowing cancer is contextualized by the serious condition that are asked to complete the (revised) Neurophysiology of Pain 374

318 has been a precursor for post-cancer pain. In many cases, Test.72 This can be done immediately after the first or second 375

319 the pain experienced by these patients has often, at least educational session, depending on the therapists’ prefer- 376

320 initially, been associated with real damage and danger and ence. 377

Please cite this article in press as: Nijs J, et al. Explaining pain following cancer: a practical guide for clinicians. Braz
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Phys Ther. 2018, https://doi.org/10.1016/j.bjpt.2018.12.003
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378 At the end of the first session, patients receive an infor- aged nerves can become more sensitive and signal the brain 435

379 mation leaflet about the neurophysiology of pain73 and are about ongoing damage. 436

380 asked to read it carefully at home. Alternatively, patients PNE plays a major role in explaining the role of the 437

381 can be asked to watch online lessons of PNE (e.g., retrain- brain in the sensation of pain. Patients need to be made 438

382 pain.org, brainman,74 etc.). Research has informed us that aware that despite ongoing tissue damage, the brain will 439

383 PNE delivered using an information leaflet only is not channel incoming stimuli and sort which gets to generate 440

384 effective.70 Other learning formats in addition to an infor- pain. In order to achieve this, one can include the follow- 441

385 mation leaflet are essential to achieve positive effects.75 A ing conversation when explaining (chemotherapy-induced) 442

386 more detailed description of how PNE can be provided is neuropathic pain: 443

387 presented elsewhere.15

Therapist (T): ‘Now you understand that the chemother- 444

apy has slightly damaged your small nerve fibers in your 445

388 Content fingers and toes, let’s have a look at this picture of a 446

kind lady who had her left breast removed surgically. 447

389 The content and pictures of the educational sessions can Breasts are full of nerve (endings), similar to the ones 448

390 be based on the book ‘Explain Pain’55 and the ‘‘Why you that are damaged in your fingers and toes. Do you think 449

391 hurt’’ therapeutic PNE system.76 PNE focuses on the nervous that surgical removal of her breast resulted in persisting 450

392 system and covers the physiology of nociception and pain, breast pain (Here we focus on phantom breast pain rather 451

393 all presented in layman’s speech, including the following than the more prevalent post-mastectomy shoulder/neck 452

394 topics: the physiology of: pain.)?’ 453

Patient (P): ‘It must have!’ 454

395 1. the neuron (receptor, axon, terminal);
396 2. the synapse (action potential, neurotransmitters, post- T: ‘That would seem reasonable, doesn’t it? Yet only a 455

397 synaptic membrane potential, chemically driven ion small minority of people receiving such breast surgery 456

398 channel); (i.e. between 9 and 25%)47,78 will experience persisting 457

399 3. descending nociceptive inhibition and facilitation (the (phantom) breast pain. Can you think of a reason why the 458

400 influence of stress, emotions, thoughts, physical activity, great majority of people having had one of their breasts 459

401 etc.); (partly) removed do not experience persisting (phantom 460

402 4. peripheral sensitization; breast) pain?’ 461

403 5. differentiation between types of pain especially acute P: ‘They reconstructed the nerves?!?’ 462
404 and chronic pain;
405 6. contributing (personal) factors in the pain experience; T: ‘Nice reasoning! Unfortunately those nerves are too 463

406 7. (in case of predominant neuropathic or central sensiti- small to reconstruct surgically. Any other idea?’ 464

407 zation pain) central sensitization (receptor field growth,

P: ‘I have no idea.’ 465
408 potentiation of the postsynaptic membrane, changes at
409 cortical and subcortical level, etc.). T: ‘Do you agree that the brain will receive similar signals 466

from the damaged nerves in her (pointing to the picture 467

410 The content is provided in a standard format, but always of the patient who had her breast removed) situation 468

411 individually tailored to the patient’s (medical) background, as the signals arising from the damaged nerves in your 469

412 pain perceptions, pain mechanisms (Fig. 1) and other pos- fingers and toes?’ 470

413 sible relevant factors identified during the intake/baseline P: ‘I don’t know . . . are people having similar damage in 471
414 assessment (Table 1). Sample PNE educational material are their finger nerves as I have, who don’t have pain?’ 472
415 freely available online in 6 languages.77
416 Contrary to PNE provided to nonspecific non-cancer T: ‘I really like the way you are reasoning right now. This 473

417 pain, the contribution of (healing or past) tissue (includ- is exactly what we need to get at. Not only the nerve 474

418 ing nerve) damage and ongoing nociception is emphasized damage will determine the pain you will or will not expe- 475

419 and explained as ‘normal’ consequences of the life-saving rience, many factors contribute to the pain. Remember 476

420 cancer treatment. This, together with explaining the neuro- that last time (during the intake) you mentioned several 477

421 physiology of nociception, is used to build the therapeutic factors that aggravate your pain, and you also mentioned 478

422 alliance and prevents the patient from suspecting that the things that can relief your pain. For instance, you men- 479

423 therapist beliefs ‘it’s all in my head’. This is important as tioned that you experience less pain when you are having 480

424 many patients are not prone for a psychological explana- fun with your friends. In such a situation, the nerve dam- 481

425 tion in the early stage of treatment. In addition, viewing age is still the same isn’t it? How can you explain that?’ 482

their pain as a side effects of life-saving treatment may

. . ..
426
483
427 aid patients in accepting their pain. Once the therapeu-
428 tic alliance is build, other (modifiable) contributing factors, The aggravating factors can then be explained as the ones 484

429 including psychological and behavioral factors and their pushing on the accelerator (Fig. 2), while the pain relieving 485

430 underlying (neuro)biology, can be explained to the patient. factors activate brain-orchestrated descending nociceptive 486

431 Initially many patients following cancer do not relate inhibition,79 which can be explained easily to patients using 487

432 nerve damage to pain. On the contrary, anecdotally many the brake (Fig. 2) or spam filter metaphor (Fig. 3). 488

433 patients wonder how they can feel pain ‘when the nerves For explaining the spam filter metaphor, the following 489

434 are cut?!?’. Hence, the first step is explaining that the dam- conversation can be included: 490

Please cite this article in press as: Nijs J, et al. Explaining pain following cancer: a practical guide for clinicians. Braz
BJPT 191 J
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Phys Ther. 2018, https://doi.org/10.1016/j.bjpt.2018.12.003
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Explaining pain after cancer 7

P: ‘No, the first thing I do is deleting all messages that 511

disinterest me.’ 512

T: ‘I do the same! And so does the brain! The brain is a 513

Inhibition fantastic computer, but it simply has not enough capacity 514

to process all input it constantly receives. Therefore, it 515

has the spam filter in the spinal cord, but it will also be 516

Facilitation highly selective to the messages passing the spam filter 517

and entering the brain. So even when a message arising 518

from your painful fingers or toes will enter your brain, 519

processing of those messages will not per se imply that 520

you will feel pain.’ 521

In case (older) patients are unfamiliar with using email, 522

one need to use an alternative metaphor to explain the 523

Figure 2 Pain neuroscience education slide illustrating how descending nociceptive inhibition, like a volume nod from 524
the brain controls two top-down systems that can either inhibit a radio than one can turn up or down. After the patient 525
(the brake) or facilitate (the accelerator) pain. understands the idea of descending inhibition and facilita- 526

tion, (modifiable) psychological and behavioral factors can 527

PAIN
brain be slowly introduced and related to the patient’s situa- 528

tion and experiences, with emphasis on how they will be 529

addressed during subsequent phases of the comprehensive 530

treatment program (e.g. stress as a pain amplifier will be 531

Pathways addressed during stress management, poor sleep by sleep 532

arising from the
Pathways going brain management; exercise therapy or graded activity will be 533
to the brain
the back gate introduced to active descending inhibition, etc.).80 534

For explaining the role of pain memories, the ‘‘pain 535

spinal card
library’’ metaphor can be introduced when explaining the 536

pain matrix. The hippocampus serves as the memory center 537

nerve of the brain, and may be considered the ‘‘brain’s library’’ 538

which may contain some pain books/memories. Yet the 539

patient sitting in front of you has experienced a lot of pain 540

over the past couple of months, implying that many more 541

Figure 3 Pain neuroscience education slide illustrating noci- pain memories were added, new books were written and the 542

ceptive pathways and using the spam filter metaphor to patient ended up with an entire pain library in the brain. 543

illustrate descending nociceptive inhibition. Nearly everything the patient does on a regular day has 544

been previously connected with a pain experience, and all 545

those memories are written down somewhere in that library. 546

491 T: ‘Do you use email?’ This makes it very easy for the brain to connect every- 547

day situations with previous pain experiences, even when 548

492 P: ‘Yes I do.’
the situation is not threatening at all. The brain is trying 549

493 T: ‘Do all emails send from anywhere in the world to your to warn the patient of being in (suspected) danger, even 550

494 email account end up in your inbox?’ though there is currently nothing to be afraid of. This is 551

similar to anticipatory nausea and vomiting in the setting 552

495 P: ‘I hope not, the spam filter should keep out inappro- of chemotherapy induced nausea and vomiting. If patients’ 553
496 priate messages including publicity.’ nausea and vomiting was not well controlled, and patients 554

497 T: ‘That’s exactly how your nervous system works. It has experience it, they may anticipate its recurrence prior to 555

498 a powerful spam filter in the back gate of the spinal cord subsequent chemotherapy or with a trigger that was present 556

499 (Fig. 3). What part of your body is in control of your spam in the environment when they experienced nausea/vomiting 557

500 filter?’ such as the smell of a perfume. 558

Further questions to be asked during the PNE session 559

501 P: ‘Perhaps the brain is?’ can be related to the patient’s understanding and opinion 560

regarding the PNE content (e.g. ‘Do you understand that 561
502 T: ‘Exactly! During the treatment program, we will teach pain and damage are not synonymous terms?’, ‘Do you think 562
503 you how you can control the spam filter in your spinal your body was recently damaged, in a way that requires 563
504 cord.’ pain as a warning signal for you?’, ‘Do you still think that 564

505 The conversation regarding the spam filter continues the pain might reflect that the cancer is returning?’, ‘Do 565

506 when explaining the pain matrix (or the dynamic pain you think that your nervous system has become more sensi- 566

507 connectome54 ): tive?’, etc.). The therapist and patient discuss these answers 567

by relating them to the PNE content. 568

508 T: ‘When you open your email inbox and you see all the The PNE will typically address past or current (cancer) 569

509 messages that have passed the spam filter, do you read treatments, including radiotherapy, surgery or chemother- 570

510 them all?’ apy and its (long-term) consequences. For instance, many 571

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572 patients who survived cancer use adjuvant endocrine ther- Funding 630
573 apy like aromatase inhibitors. Unfortunately, aromatase
574 inhibitors often result in debilitating side effects like pain: This work is partially funded by the Berekuyl Academy Chair, 631
575 approximately 50% of breast cancer survivors on aromatase funded by the European College for Decongestive Lymphatic 632
576 inhibitor therapy report musculoskeletal pain.81 Such mus- Therapy, the Netherlands, and awarded to Jo Nijs, Vrije Uni- 633
577 culoskeletal pain remains even after stopping the adjuvant versiteit Brussel, Belgium. 634
578 endocrine therapy. The reason for this common side effect
579 of aromatase inhibitors is still an active area of research,
Conflicts of interest 635
580 and advances have been made. Animal work suggests that
581 aromatase inhibitors selectively target the transient recep-
582 tor potential ankyrin 1 (TRPA1) channel, a major pathway JN has co-authored a Dutch book for clinicians on pain neu- 636

583 in pain transmission and neurogenic inflammation.82 Aro- roscience education, but the royalties for that book are 637

584 matase inhibitors activate TRPA1 channels in nociceptors, collected by the Vrije Universiteit Brussel and not him per- 638

585 resulting in the release of sensory neuropeptides (i.e. neuro- sonally. PvW co-authored a Dutch book for clinicians on PNE 639

586 inflammation) and mechanical hypersensitivity, together and receives royalties. Besides that, the authors have no 640

587 corresponding to a picture of generalized peripheral sensi- conflict of interest to disclose. 641

588 tization. Indeed, TRPA1 is not only expressed on the distal,

589 but also on the central endings of the primary afferent noci- Acknowledgements 642

590 ceptive fibers, located within the spinal dorsal horn.83 When
591 explaining this to patient, it often suffices to detail that: This work is partially funded by the Berekuyl Academy Chair, 643

funded by the European College for Decongestive Lymphatic 644

592 - the adjuvant endocrine therapy sensitizes the nerve end- Therapy, the Netherlands, and awarded to Jo Nijs, Vrije Uni- 645

593 ings in the musculoskeletal system rather than damaging versiteit Brussel, Belgium. 646

594 any tissues;

595 - the increased nerve sensitivity rather than any ongoing References 647
596 tissue damage explains the pain;
597 - the adjuvant endocrine therapy increases disease free sur- 1. Ghoncheh M, Mirzaei M, Salehiniya H. Incidence and mortality 648
598 vival time,84,85 and should therefore be continued. of breast cancer and their relationship with the Human Devel- 649
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599 Conclusion 2. Krok-Schoen JL, Fisher JL, Baltic RD, Paskett ED. White- 652
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600 PNE has been suggested repeatedly as an important add to and survival among adults aged 85 years and older in 654

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602 lowing cancer.13,80 The present paper explained how PNE can 2016;25(11):1517---1523. 656

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Please cite this article in press as: Nijs J, et al. Explaining pain following cancer: a practical guide for clinicians. Braz
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Phys Ther. 2018, https://doi.org/10.1016/j.bjpt.2018.12.003