Guide to Pain Management in Low-Resource Settings

What prophylactic therapy               
is available in migraine?
Prophylactic antimigraine treatment must be individ-
ually tailored to each patient, taking into account the 
migraine subtype, the ensuing disability, the patient’s 
history and demands, and the associated disorders. A 
prophylactic treatment is also useful to prevent the 
transformation of episodic migraine into chronic dai-
ly headache with analgesic overuse (medication over-
use headache).
A major drawback of most classical prophylac-
tics (beta-blockers devoid of intrinsic sympathomimetic 
activity, valproic acid, Ca
2+
 antagonists, antiserotonin-
ergics, and tricyclics), which have all on average a 50% 
effi
  cacy score, is the occurrence of side eff ects. If the 
initial trial is successful in reducing frequency of attacks 
without causing signifi cant chronic side eff ects,  then 
the preventive therapy may be continued for 6 months. 
After 6 months, the dose is gradually decreased before 
stopping the treatment. If the treatment is not success-
ful, dosing of the medication should be increased up to 
the maximum allowed, or a new preventive treatment 
should be initiated.
In recent years, some new prophylactics with 
less side eff ects have been studied. Well-tolerated, but 
poorly eff ective in comparison to the classical prophylac-
tics, are high-dose magnesium or cyclandelate. A novel 
preventive treatment for migraine is high-dose (400 
mg/d) ribofl avin, which has an excellent effi
  cacy/side-
eff ect ratio and probably acts by improving the mito-
chondrial phosphorylation potential. Coenzyme Q
10
 (100 
t.i.d.), another actor in the mitochondrial respiratory 
chain, is also eff ective in migraine prophylaxis. Lisinopril 
(10 mg b.i.d.), an inhibitor of angiotensin-converting en-
zyme, and even more so, candesartan (16 mg b.i.d.), an 
angiotensin II inhibitor, well-known for the treatment of 
hypertension, were found useful in migraine.
Recent preliminary but encouraging results 
with novel antiepileptic compounds such as gabapentin 
need to be confi rmed in large randomized controlled 
trials, whereas topiramate was found eff ective in several 
placebo-controlled trials. Lamotrigine is up to now the 
only preventive drug that has been shown eff ective for 
migraine auras, but not for migraine without aura. Non-
pharmacological and herbal treatments are increasingly 
subject to controlled studies, and some, like butterbur 
(Petasites), were found clearly more eff ective than pla-
cebo. Several nondrug therapies (such as biofeedback 
and psychologically based interventions) have proven 
effi
  cacy in migraine prophylaxis.
How is the pharmacological 
prophylaxis therapy in         
migraine selected?
Interestingly, the recommendations for prophylac-
tic treatment of migraine diff er around the world. 
Beta-blockers and valproate are usually among the 
fi rst choices. Th
 e choice of drug should neverthe-
less be individualized according to the drug’s side-ef-
fect profi le. For example, older patients might benefi t 
from the antihypertensive properties of beta-blockers, 
while younger ones may suff er considerably from beta-
blocker-induced sedation.
Apart from the drugs in the list, there are other 
pharmacological options with weaker evidence, including 
magnesium (24 mmol daily, especially for migraine asso-
ciated with the menstrual period), Petasites (butterbur), 
Tanacetum parthenium (feverfew), candesartan (16 mg 
daily), coenzyme Q
10
 (100 mg t.i.d.) and ribofl avin  (400 
mg daily).
Table 5
Selection criteria for prophylactic pharmacological treatment in 
migraine
Drug and Dose 
Selected Adverse Eff ects
Valproic acid, 500–1000 
mg nightly (sustained 
release)
Liver toxicity, sedation, nausea, 
weight gain, tremor, teratogenic-
ity, possible drug toxicity, hair loss, 
drowsiness
Beta-blockers
Propranolol, 40–240 mg
Bisoprolol, 2.5–10 mg
Metoprolol, 50–200 mg
Reduced energy, tiredness, postural 
symptoms, contraindicated in asthma
Flunarizine, 5–10 mg daily
Drowsiness, weight gain, depression, 
parkinsonism
Topiramate, 25–100 mg 
twice daily
Paresthesias, fatigue, nausea, cogni-
tive dysfunction
Amitriptyline, 25–75 mg 
nightly
Weight gain, dry mouth, sedation, 
drowsiness
Methysergide, 1–4 mg daily Drowsiness, leg cramps, hair loss, ret-
roperitoneal fi brosis (1-month drug 
“holiday” required every 6 months)
Gabapentin, 900–3600 mg 
daily
Dizziness, sedation
Lisinopril, 10–20 mg daily
Cough

218
Arnaud Fumal and Jean Schoenen 
What is essential to know about 
tension-type headache?
Tension-type headache (TTH) is an ill-defi ned  and 
heterogeneous syndrome, of which diagnosis is mainly 
based on the absence of features found in other head-
ache types such as migraine (see Tables 4 and 5 for diag-
nostic criteria). It is thus above all a “featureless” head-
ache, characterized by nothing but pain in the head. 
Th
  e diagnostic problem most often encountered is to 
discriminate between TTH and mild migraines. TTH 
is the most common form of headache, but it receives 
much less attention from health authorities, clinical re-
searchers, or industrial pharmacologists than migraine. 
Th
  at is because most persons with infrequent or fre-
quent TTH never consult a doctor; treat themselves, if 
necessary, with over-the-counter analgesics. Howev-
er, chronic TTH, which causes headache ≥15 days per 
month represents a major health problem with an enor-
mous socioeconomic impact. In a population-based 
study, the lifetime prevalence of tension-type headache 
was 79%, with 3% suff ering from chronic TTH, i.e., 
headache ≥15 days per month.
It still is a matter of debate whether the pain in 
TTH originates from myofascial tissues or from central 
mechanisms in the brain. Research progress is ham-
pered by the diffi
  culty in obtaining homogeneous pop-
ulations of patients because of the lack of specifi city 
of clinical features and diagnostic criteria. Th
 e present 
consensus, nonetheless, is that peripheral pain mecha-
nisms are most likely to play a role in infrequent epi-
sodic TTH and frequent episodic TTH, whereas central 
dysnociception becomes predominant in chronic TTH.
Simple analgesics (i.e., ibuprofen 600 to 1200 
mg/d) are the mainstay of treatment of episodic TTH. 
Combination analgesics, triptans, muscle relaxants, 
and opioids should not be used, and it is crucial to even 
avoid frequent and excessive use of simple analgesics to 
prevent the development of medication overuse head-
ache. Prophylactic pharmacotherapy should be consid-
ered in patients with headaches for more than 15 days 
per month (chronic TTH). A prophylactic treatment is 
useful to prevent the transformation of episodic TTH 
into medication overuse headache. Th
  e tricyclic antide-
pressant amitriptyline is the drug of fi rst choice for the 
prophylactic treatment of chronic TTH, but nonphar-
macological management strategies (relaxation, bio-
feedback, physical therapy) are equally eff ective.  Th
 e 
initial dosage of tricyclics should be low: 10–25 mg 
of amitriptyline at bedtime. Many patients will be satis-
fi ed by such a low dose. Th
  e average dose of amitripty-
line in chronic TTH, however, is 75–100 mg per day. If 
a patient is insuffi
  ciently improved on this dose, a trial of 
higher doses of amitriptyline is warranted. If the head-
ache has improved by at least 80% after 4 months, it is 
reasonable to attempt discontinuation of the medication. 
Decreasing the daily dose by 20–25% over 2–3 days may 
avoid rebound headache. Th
  e best results are obtained 
by combining tricyclics with relaxation therapy.
What is essential to know about 
cluster headache and other 
trigeminal autonomic cephalalgias?
Trigeminal autonomic cephalalgias (TACs) are a group 
of rare primary headache syndromes that include clus-
ter headache, paroxysmal hemicrania, SUNCT (short-
lasting unilateral neuralgiform headache attacks with 
conjunctival injection and tearing), and SUNA (short-
lasting unilateral neuralgiform headache attacks with 
cranial autonomic symptoms). Although rare, they are 
important to recognize because of their excellent but 
highly selective response to treatment. Th
  ey share the 
same features in their phenotype of headache attacks, 
which is a severe unilateral orbital, periorbital, or tem-
poral pain, with associated ipsilateral cranial autonomic 
symptoms, such as conjunctival injection, lacrimation, 
nasal blockage, rhinorrhea, eyelid edema, and ptosis. 
Th
  e distinction between the syndromes is made on du-
ration and frequency of attacks.
As cluster headache (CH) is the commonest of 
the TACs, we will describe only this kind of headache in 
the present chapter. CH has a prevalence of about 0.3%, 
and male-female ratio of 3.5–7:1. Th
 e attacks of CH 
are stereotypical, being severe or excruciating, lasting 
15–180 minutes, occurring once every other day up to 
eight times per day, and associated with ipsilateral au-
tonomic symptoms. In most patients, CH has a striking 
circannual and circadian periodicity. Diagnosis is based 
on IHS criteria for the phenotype of attacks, but an MRI 
of the brain with contrast should be performed in order 
to rule out a secondary/symptomatic CH.
Cluster headache patients should be advised to 
abstain from taking alcohol during the cluster period. 
Because the pain of CH builds up so rapidly, abortive 
agents have to act quickly to be useful. By far the most 
effi
  cient one is a subcutaneous injection of sumatriptan 
6 mg. Inhalation of 100% oxygen, at 10 to 12 L/minute 

Headache
219
via a nonrebreathing facial mask for 15 to 20 minutes, 
can be eff ective in up to 60–70% of attacks, but pain 
frequently recurs. Th
 e aim of the preventive therapy 
is to produce a rapid remission of the disorder and to 
maintain that remission with minimal side eff ects  un-
til the cluster bout is over according to its natural his-
tory, or for a longer period in patients with chronic CH. 
Steroids are very eff ective in interrupting a bout. Sub-
occipital injections of long-acting steroids should be 
preferred to oral treatment, to lessen the risk of “corti-
co-dependence.” Verapamil is the next preventive drug 
of choice, but lithium, topiramate, methysergide, or cor-
ticosteroids can also be used. Functional imaging data 
suggest the hypothalamus to be the origin for CH.
Can headache medication         
cause headache?
Overuse of acute medication is the most frequent factor 
associated with the transformation of episodic migraine 
into chronic daily headache. Th
  e latter is called “medica-
tion overuse headache” (MOH) in the 2nd edition of the 
International Classifi cation of Headache Disorders (ICHD-
II, 2004). It is classifi ed as a secondary headache disorder, 
which may evolve from any type of primary headache, but 
mainly from episodic migraine, and in a lower proportion 
in tension-type headache. MOH is a disabling health prob-
lem, which may aff ect 1–2% of the general population.
Th
  e most effi
  cient treatment for MOH is abrupt 
drug withdrawal and immediate prescription of a pre-
ventive drug (an antimigraine agent if the primary head-
ache is a migraine, or tricyclics in case of TTH), but 
there are no studies comparing diff erent strategies. Th
 ere 
are thus no clear, worldwide accepted guidelines regard-
ing modality of withdrawal or treatment of withdrawal 
symptoms. Oral prednisone, acamprosate, tizanidine, 
clomipramine, and intravenous dihydroergotamine were 
found useful for withdrawal headaches, but results are 
confl icting, for example, prednisone shows both posi-
tive and negative results. It seems clear that after the fi rst 
2-week physical withdrawal period, comprehensive long-
term management of the biopsychosocial problem of 
these patients is necessary to minimize relapse.
Pearls of wisdom
•  Recurrent headache disorders impose a substan-
tial burden on individual headache suff erers,  on 
their families, and on society.
•  Although headache is one of the most common 
reasons for patients to consult their doctor, and 
despite its enormous impact, it is still under-rec-
ognized and undertreated.
•  Inaccurate diagnosis is probably the most com-
mon reason for treatment failure. A systematic 
approach to classifi cation and diagnosis is there-
fore essential both for clinical management and 
research.
•  Improvements in treatment have been less dra-
matic than remarkable revelations from basic and 
clinical research on headaches.
•  Finally, while the eff ective newer treatments are 
quite expensive, e.g., newer antiepileptics and 
triptans, older drugs are still available everywhere 
with a good benefi t-cost ratio: NSAIDs (for acute 
treatment) and beta-blockers and/or ribofl avin 
(for prophylactic treatment) in migraine, and oxy-
gen (for acute treatment) and verapamil (for pro-
phylactic treatment) in cluster headache.
References
[1]  Cohen AS, Matharu MS, Goadsby PJ. Trigeminal autonomic cephalal-
gias: current and future treatments. Headache 2008;47:969–80.
[2]  Colas R, Munoz P, Temprano R, Gomez C, Pascual J. Chronic daily 
headache with analgesic overuse: epidemiology and impact on quality 
of life. Neurology 2004;62:1338–42.
[3]  Ferrari MD, Roon KI, Lipton RB, Goadsby PJ. Oral triptans (serotonin 
5-HT
1B/1D
 agonists) in acute migraine treatment: a meta-analysis of 53 
trials. Lancet 2001;358:1668–75.
[4] Fumal A, Schoenen J. Current migraine management—patient accept-
ability and future approaches. Neuropsychiatr Dis Treat 2008;4:1043–
57.
[5]  Fumal A, Schoenen J. Tension-type headache. Where are we? Where do 
we go? Lancet Neurol 2008;7:70–83.
[6]  Goadsby P. Recent advances in the diagnosis and management of mi-
graine. BMJ 2006;332:25–9.
[7]  International Headache Society. Th
 e International Classifi cation  of 
Headache Disorders. 2nd edition (ICHD-II). Cephalalgia 2004;24(Suppl 
1):1–160.
[8] Mateen 
FJ, Dua T, Steiner T, Saxena S. Headache disorders in de-
veloping countries: research over the past decade. Cephalalgia 
2008;28:1107–14.
Websites
International Headache Society (IHS): http://www.i-h-s.org/
Following the listing by the World Health Organization of the world’s 100 
poorest countries (British Medical Journal 2002;324:380), IHS off ers Associ-
ate Membership free to individuals living in those countries who qualify for 
Ordinary Membership. Associate Membership carries the responsibilities to 
the Society of Ordinary Membership (other than payment of the member-
ship fee), but off ers limited benefi ts. Th
  ese include on-line access to the 
Society’s journal Cephalalgia.
American Headache Society (AHS): www.americanheadachesociety.org/
World Headache Alliance (WHA): http://www.w-h-a.org/

221
Guide to Pain Management in Low-Resource Settings, edited by Andreas Kopf and Nilesh B. Patel. IASP, Seattle, © 2010. All rights reserved. Th
  is material may be used for educational 
and training purposes with proper citation of the source. Not for sale or commercial use. No responsibility is assumed by IASP for any injury and/or damage to persons or property 
as a matter of product liability, negligence, or from any use of any methods, products, instruction, or ideas contained in the material herein. Because of the rapid advances in the 
medical sciences, the publisher recommends that there should be independent verifi cation of diagnoses and drug dosages. Th
  e mention of specifi c pharmaceutical products and any 
medical procedure does not imply endorsement or recommendation by the editors, authors, or IASP in favor of other medical products or procedures that are not covered in the text.
Guide to Pain Management in Low-Resource Settings
Fereydoun Davatchi
Chapter 29
Rheumatic Pain
What is rheumatology?
Rheumatology is a subspecialty of internal medicine 
dealing with bone and joint diseases (connective tis-
sue and related tissue disorders of bone, cartilage, ten-
dons, ligaments, tendon sheets, bursae, muscles, etc.). 
Although modern rheumatology is based on advanced 
molecular biology, immunology, and immunogenetics, 
the daily practice and routine diagnosis is mainly clini-
cal and based on symptoms and signs. In the majority 
of cases, laboratory tests and imaging have a confi rma-
tory role, instead of being mandatory. Simple tests, such 
as complete blood count (CBC), erythrocyte sedimen-
tation rate (ESR), C-reactive protein (CRP), rheumatoid 
factor (RF), uric acid, and urinalysis, are suffi
  cient  in 
many cases. Sophisticated investigations are rarely man-
datory in routine practice. Th
  e same is true regarding 
elaborate imaging technics.
How are rheumatological      
diseases classifi ed?
They are divided in three groups: articular, extra-ar-
ticular, and bone diseases. Articular manifestations 
can be divided into six categories: inflammatory, 
mechanical, metabolic, neurological, infectious, and 
tumoral disorders. Extra-articular manifestations 
are also called soft tissue rheumatism (tendonitis, 
tenosynovitis, bursitis, etc.). Bone diseases are divid-
ed into metabolic (osteoporosis, osteomalacia), infec-
tious, tumoral (benign, malignant, metastatic), and ge-
notypic malformations.
What is the connection between 
rheumatology and pain?
The most important symptom in rheumatology is 
pain. The pain can be inflammatory, mechanical, or 
continuous. Inflammatory pain occurs during rest 
and disappears or improves gradually with activity. 
It is accompanied by some degree of stiffness, espe-
cially in the morning when the patient wakes up. Me-
chanical pain appears with activity, increases gradu-
ally, and disappears with rest. It can be accompanied 
by gelling pain, which resembles inflammatory pain, 
but is of very short duration (a few minutes or less). 
Pure continuous pain is rare; usually one can find an 
inflammatory or mechanical feature. Joint swelling is 
the second most important symptom in rheumatol-
ogy. It can be due to either effusion or synovial hy-
pertrophy. Bony enlargement of the joint (bone hy-
pertrophy) is the differential diagnosis. Limitation of 
joint movement is an indicator of joint involvement. 
Abnormal movement is an indicator of joint disloca-
tion (cartilage destruction, ligament tear, and epiphy-
seal collapse).

222
Ferydoun Davatchi
How do you diagnose                           
a rheumatological disease?
Th
  e characteristics of each joint, the chronology of the 
symptoms, the number and location of involved joints, 
and the pattern of involvement are usually enough to 
suspect a diagnosis, or better, to make a diagnosis. In 
many cases (soft-tissue rheumatisms, low back pain, or 
mechanical cervical pain), no laboratory investigation 
is necessary. In others, simple laboratory tests as men-
tioned above will be suffi
  cient. When necessary, plain 
X-rays will often give suffi
  cient information.
What are the principles of treatment?
Although treatment has made great advances in the last 
decade (biological agents, sophisticated immune modu-
lators, etc.), in many cases good advice and minimal 
medications will control the patient’s pain effi
  ciently. 
Th
  e majority of low back pain will respond well to a few 
days of rest and anti-infl ammatory drugs. After resting, 
patients have to be taught how to strengthen their mus-
culature with adequate exercises and must be advised 
about maintaining daily activities. Th
  e same is true for 
cervical pain, osteoarthritis, and many of the soft-tissue 
rheumatisms. It is a false idea that mechanical pain, like 
osteoarthritis, needs analgesics or anti-infl ammatory 
drugs for a long time or forever. Continuous use of an-
algesics will lead to more cartilage damage in the joint, 
while correct use of the joint will help to arrest or slow 
down the cartilage degradation. If nonsteroidal anti-
infl ammatory drugs (NSAIDs) are necessary, there is 
no need to go for the new generation of COX-2 drugs, 
which are very expensive. Indomethacin and diclofenac 
are cheap, eff ective, and widely available. New therapies, 
mainly biological agents, have changed the outcome 
of crippling rheumatic disease. Unfortunately, they are 
very expensive and not aff ordable in many places. How-
ever, tried and true medications, available since the 
mid-20th century, can still make a vast diff erence, if cor-
rectly combined and used. Some of them are relatively 
aff ordable (e.g., chloroquine, prednisolone).
What do you need to know        
about osteoarthritis?
Osteoarthritis (OA) is the mechanical disorder par 
excellence. It is due to degeneration of the cartilage 
and may be primary (related to age or menopause) 
or secondary (related to mechanical eff ort, metabolic 
disorders, or genetic malformation, infl ammatory  ar-
thritis, infectious arthritis). It is seen in 9.6% of the 
population aged 15 or older in Asian-Pacifi c countries 
[1]. Th
  e starting age depends mainly on the joint, with 
individual variation, which is probably due to varia-
tion in genetics. At the beginning, OA may not be 
painful, or the pain may be episodic. Laboratory tests 
are unnecessary. CBC, ESR, CRP, RF, uric acid, and in-
fectious diseases tests, mainly Wright for brucellosis 
and PPD (purifi ed protein derivative) for tuberculosis, 
are normal.
Plain X-ray is not necessary for the diagnosis, 
helping essentially to demonstrate the severity of car-
tilage destruction. Th
 e radiographic signs appear late 
(months or years after the onset) and are mainly joint 
space narrowing and osteophytes.
Th
  ere is no specifi c treatment to cure or even 
stop the progress of OA. Pain, on the contrary to 
what the patient thinks, is acting in his/her favor. Pain 
shows what activity is harmful to the joint and how 
much activity it can aff ord without interfering with the 
normal physiology of the cartilage. Pain-killing tech-
niques are usually harmful for the joint, unless they 
are given concomitantly with rest. In many instances, 
there is no need for complete rest or medication. Ex-
plaining the physiology of pain is the best treatment 
for the prevention of fast degradation of the joint. Joint 
activity is permitted to the degree that pain is not too 
severe. In severe cases, anti-infl ammatory drugs, ei-
ther NSAIDs or steroids, are preferable as analgesics. 
Th
  ey are given for 2 to 3 weeks (150 mg indomethacin 
or diclofenac, 15 mg prednisolone), along with moder-
ate joint rest. After this period, medication is stopped, 
and the patient is advised about adequate joint activity. 
Exercise to improve muscle strength is very important, 
which by improving joint physiology helps to slow 
down the disease process.