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NEWSLETTER OF THE NORTH BRITISH PAIN ASSOCIATION - SPRING 2004

FROM THE EDITOR
Welcome to the Spring 2004 edition of
Threshold, brought to you with the support of
Pfizer pharmaceuticals. In this issue, as well
as the regular features, there are two articles
submitted by NBPA members. I am very
grateful to Gail Gillespie, the current Glasgow
Pain Management Fellow, who has compiled
an up to date report on NSAIDs and the new
generation of COX 2 inhibitors. In addition,
Claire Dunlop, Senior Chartered
Physiotherapist at the Astley Ainslie pain
management programme has written an
account of the Fourth Congress of the
European Federation of the International
Association for the Study of Pain, held in
Prague, which she attended in September
2003. Her visit was supported by a traveling
grant from the NBPA and we are delighted to
hear that she found the conference so useful
and interesting.
I hope you enjoy the rest of this issue.
Please send any suggestions or submissions
to me at the address below.
Dr Colin P. Rae,
Department of Anaesthesia,
Stobhill Hospital,
133 Balornock Road,
Glasgow,
G21 3UW.
Tel no 0141 201 3005.
Fax no 0141 201 4167.
Email colin.rae@northglasgow.scot.nhs.uk
Website www. nbpa.org.uk or www.nbpa.ac.uk
DATES FOR YOUR DIARY
Winter Scientific Meeting
Friday 5th November 2004
Spring Scientific Meeting
Friday 6th May 2005
Professor Iain McInnes
and Dr. Donald McMillan
Professor of Experimental Medicine at
Glasgow Royal Infirmary, started with an
overview of the role that inflammation and the
immune system play in various disease
processes. He concentrated initially on
rheumatoid arthritis (RA), which as well as
causing a great deal of morbidity, has a
significant 5 year mortality if more than thirty
joints are affected. Recent research has
concentrated on the role of cytokines,
interleukins and TNFa in the inflammatory
process within rheumatoid joints. He finished
with the optimistic note that perhaps
rheumatoid arthritis will be a curable rather
than a managed disease, within the next
decade.
Drs Susan Nimmo and Michael Basler
of PHN cases are in the over 60-age group.
Only two risk factors for the development of
PHN have been identified; increasing age and
the presence of prodromal symptoms. The
level of varicellar antibodies or cytokines does
not influence the incidence of PHN. There
does seem to be a seasonal variation in the
incidence of PHN, which might be explained
by ultra violet light suppressing cell-mediated
immune responses.
Dr Janet Braidwood, Sister Anne Kelly
and Dr. Dick Davidson Lamb
Dr. Donald McMillan from the University
Department of Surgery at Glasgow Royal
Infirmary gave the third lecture, “An
Inflammatory View of Cancer”. His main area
of research has been into the weight loss and
cachexia associated with cancer. He explained
that you could think of a tumour as a wound
that will not heal. The traditional view is that
tumours are associated with an increased
energy demand and produce toxins that cause
anorexia and thus cachexia. The increased
resting energy expenditure may explain the
fatigue suffered by cachectic patients. More
recently, the view is emerging that cancer
causes both a chronic inflammatory response
and a release of products which together result
in metabolic abnormalities such as lipolysis,

Professor Mary Norval, from the

REPORT FROM WINTER
SCIENTIFIC MEETING
Due to shortage of space, this is a fairly
succinct report of the Winter meeting, which
is in no way a reflection of the quality of the
talks or my note taking. The day was kindly
supported by Pfizer, Napp, MSD and Janssen
Cilag. The theme was “Pain – An
Inflammatory View”. Professor Iain McInnes,
Department of Medical Microbiology at the
University of Edinburgh, followed with a
virologists view on post herpetic neuralgia
(PHN). She initially reviewed the cause,
clinical presentation, epidemiology and
pathophysiology of PHN. 200,000 people in
the United Kingdom have PHN at any one
time. Pain usually resolves 4-6 weeks after the
rash disappears. Approximately 10-15% of Professor Iain McInnes, Dr. Mick Serpell
patients will develop PHN and more than 50% and Professor Mary Norval
protein loss and anorexia. The systemic
inflammatory response is the same whatever
the type of tumour and is at a level equivalent
to the response following major surgery. The
important difference is that the response is
sustained. It has been demonstrated that the
greater the C reactive protein level (a marker
of the inflammatory response), the poorer the
prognosis of the patient.
The afternoon session, chaired by Nicola
Stuckey, was an afternoon of contrasts. It
began with an excellent lecture by Professor
Daniel McQueen of the Department of
Pharmacology at the University of Edinburgh
and NBPA council member. He gave a
fascinating overview of COXs 1-3 and their
role in the inflammatory response, covering
the mechanism of action of familiar and new
agents.
As an experiment, the day finished with a
debate. The motion was “This house believes
that the bio-psychosocial model has outlived
its use”. Speaking for the motion was
Professor Marie Johnston from Aberdeen and
against Dr. David Craig from Glasgow. The
discussion was lively although the speakers
had trouble disagreeing on some aspects of the
discussion, the general feeling being that the
biopsychosocial model had not outlived its
use.
NEWS FROM COUNCIL
At the last council meeting, several council
members intimated their intention to stand
down from council. Those stepping down are
Dr. Ruhy Parris, Secretary, Dr. Alan Semple,
Treasurer and Sister Anne Kelly, nursing and
East of Scotland representative. All have
worked hard on behalf of the NBPA
membership over several years. Special
mention must go to Anne who is the longest
serving council member and whose ideas,
sense of humour and hard work will be sorely
missed. Nominations for replacements will be
sought at the AGM in May.
Council would like to thank Bernhard
Frank from Newcastle for donating £250 to
purchase the NBPA website address from
Newcastle University. At present both
addresses above will direct you to the NBPA
site.
There have been further discussions about
the NBPA annual essay competition. It may
be that the prize money will be increased for
the 2005 competition so all interested parties
should pay attention on May 7th.
Many of you will be aware that Professor
McEwan has been asked by the Scottish
Executive to survey the current status of Pain
Services in Scotland. All submissions have
been sent and we await his report with interest.
The Cross Party Working Group on
Chronic pain at the Scottish Executive
continues to meet, convened by Dr. Jean
Turner MSP. The fact that there is no
representation from the NBPA on this group
was highlighted at the last council meeting.
Following this, the convenor, Dr. Jean Turner
has approached council members and asked
if representatives could attend, and make a
presentation to, the next meeting of the group,
towards the end of April. Any developments
as a result of this will be circulated to
members.
NSAIDS and COXIBS
- What’s new?
Dr. Gail Gillespie
Specialist Registrar in Pain Management
Glasgow
The discovery of cyclooxygenase (COX)-2
provided the rationale for the development of
the new class of non-steroidal anti-
inflammatory drugs (NSAIDs), the selective
COX-2 inhibitors or ‘Coxibs’. Their aim was
to reduce toxicity associated with the
administration of NSAIDs, by virtue of their
COX-1 sparing effects.
First Generation Coxibs
Rofecoxib and celecoxib were the first
selective coxibs. They are both effective
means of acute pain relief.(1) Celecoxib is
7.5 times more selective for COX-2 than
COX-1. Rofecoxib is 35 times more selective
for COX-2. (2)
Second Generation Coxibs
Recently, other selective coxibs with
different COX-1/COX-2 selectivity and
pharmacokinetic features have been
developed: valdecoxib, parecoxib, etoricoxib
and lumiracoxib. Valdecoxib is twice as
COX-2 selective as celecoxib in vitro. The
clinical relevance of this is unclear.
Parecoxib, a pro-drug of valdecoxib, is the
only injectable Coxib.
Lumiracoxib is the most selective COX-2
inhibitor in vitro being 400 times more
selective for COX-2. It is unusual in that it is
the only acidic coxib. Theoretically, this
should allow high concentrations to penetrate
inflammatory sites and thus improve efficacy.
This is still to be clarified in vivo.
GI toxicity:
NSAID-associated GI side effects represent
25% of all drug side-effects reported to the
FDA. 2-4% of chronic NSAID users will
develop upper GI bleeding, symptomatic
ulceration or perforation each year. (3) Coxibs
have been demonstrated to halve the incidence
of serious upper GI events as compared to non-
selective NSAIDs. (4)(5)
Cardiovascular toxicity:
In theory, there are pathophysiological
mechanisms which could explain why
selective cox-2 inhibition might increase
cardiovascular risk: namely, that coxibs may
have prothrombotic activity by tipping the
balance in favour of thrombaxane A2 over
prostacyclin, resulting in an increase tendency
for vascular occlusion and tissue ischaemia.
The annualized myocardial infarction rate for
Coxibs in both the VIGOR(6) and the
CLASS(7) trials was higher with roficoxib and
celecoxib than placebo. However, aspirin
therapy was withheld in the VIGOR study, and
larger studies using rofecoxib have shown no
increase in MI rates. Therefore, the actual level
of evidence demonstrating an increased risk
is weak.
It seems that highly selective coxibs may
increase the risk for cardiothrombotic events
only in those at-risk patients who are not
taking aspirin. The best way of safely co-
administering aspirin and coxibs in this group
of patients is as yet unknown. Further studies
are required to look specifically at cardiac risk.
Overall:
The results of clinical trials have shown
that coxibs have a comparable clinical efficacy
and renal toxicity and an improved GI safety
versus nonselective NSAIDs. Whether the
different pharmacodynamic and
pharmacokinetics features of the various
coxibs will produce detectable differences in
efficacy and toxicity remains to be evaluated
in appropriate comparative randomized
clinical studies.
Bandolier describes the ‘Oxford league
table of analgesics in acute pain’.
This is a table based on the number-
needed-to-treat (NNT) that was constructed
from information gathered from systematic
reviews of randomized double-blind placebo-
controlled trials.
Outcome was 50% or more pain relief over
4-6hrs using validated standardized pain
measurements.
Although it is useful as a guide, we must
be circumspect in the conclusions drawn from
this league table. The main problem is that
the size of the trial will impact on the accuracy
of the results. Small trials or data sets will not
yield accurate estimations of efficacy.
References:
(1) Single dose oral celecoxib for post-operative
pain. Cochrane database of Systematic
Reviews1, 2003 Barden J et al.
(2) Cox-2 inhibitors: today and tomorrow.
American Journal of the Medical Sciences.
323(4):181-9, 2002 Apr.
(3) Best Practice & Research, Clinical
Anaesthesiology vol.17 No.1, p91-110
2003. Schug S et al.
(4) Rofecoxib for rheumatoid Arthritis
Cochrane Database of Systematic Reviews
1, 2003 Garner S et al
(5) Celecoxib was similar to naproxen for
rheumatoid arthritis with fewer endoscopic
ulcers. ACP journal club 132(3)p96 2000
(6) Bombardier C, Laine L, Reicin A, et al.
Comparison of upper gastrointestinal
toxicity of rofecoxib and naproxen in
patients with rheumatoid arthritis.VIGOR
Study Group. N Engl J Med 2000; 343:
1520–8.
(7) Silverstein FE, Faich G, Goldstein JL, et al.
Gastrointestinal toxicity with celecoxib vs
nonsteroidal anti-inflammatory drugs for
osteoarthritis and rheumatoid arthritis: the
CLASS study: A randomized controlled
trial.Celecoxib Long-term Arthritis Safety
Study. JAMA 2000; 284: 1247–55.
 League Table of Coxibs may result in a selective attentional bias
towards pain related information and/or
The full version of this league table, including individual trial size, pronounce the experience of pain via
can be found at www.jr2.ox.ac.uk cognitive/emotional appraisal. An important
message for the clinical situation is to avoid
Analgesic NNT Lower confidence Higher confidence advice that could trigger anticipation of pain.
interval interval
Etoricoxib 180mg 1.2 1.1 1.4 “Hypervigilance Mediates the
Association Between Fear and Pain”.
Etoricoxib 120mg 1.5 1.3 1.7
Experimental results showed that individuals
Etoricoxib 240mg 1.5 1.2 1.8 with high pain related fear detected low-
Valdecoxib 40 mg 1.6 1.4 1.8 intensity, ambiguous somatosensory stimuli
Valdecoxib 20 mg 1.7 1.4 2.0 faster, had more difficulty in disengaging from
Diclofenac 100mg 1.9 1.6 2.2 potentially threatening somatic stimuli, and
Celecoxib 400mg 1.9 1.6 2.3 had decreased attentional capacity for
Etoricoxib 60mg 2.0 1.6 2.8 cognitive task performance compared to
controls. With high fear patients, distraction
(Paracetamol 1000mg+Codeine 60mg 2.2 1.7 2.9)
was shown not to affect pain tolerance or
Parecoxib 40 mg (iv) 2.2 1.8 2.7 intensity in an experiment carried out with
Rofecoxib 50mg 2.3 2.0 2.6 iced water. The overall conclusion was that
Diclofenac 50mg 2.3 2.0 2.7 levels of pain related fear were associated with
Naproxen 440mg 2.3 2.0 2.9 pain intensity. There was evidence that high
Ibuprofen 600mg 2.4 2.0 4.2 fear patients show increased attention to pain.
“New Treatments of Rheumatoid
Ibuprofen 400mg 2.4 2.3 2.6
Arthritis” was a plenary session. In RA it has
Naproxen 550mg 2.6 2.2 3.2
been found that damage in joints is much more
Ketorolac 10mg 2.6 2.3 3.1 widespread than was first thought, therefore,
Ibuprofen 200mg 2.7 2.5 3.1 treatment is now based on early suppression
Piroxicam 20mg 2.7 2.1 3.8 of disease activity (and prevention of
Diclofenac 25mg 2.8 2.1 4.3 irreversible joint damage) as soon as possible
Morphine 10mg (intramuscular) 2.9 2.6 3.6 after diagnosis, irrespective of the kind or
number of drugs indicated. It has become clear
Parecoxib 20mg (iv) 3.0 2.3 4.1
that the cytokines TNFa and IL1 play an
Naproxen 220mg/250mg 3.1 2.2 5.2 important role in the inflammatory process of
Ketorolac 30mg (im) 3.4 2.5 4.9 R.A. Treatments have been specifically
Paracetamol 500mg 3.5 2.2 13.3 developed to block these proinflammatory
Celecoxib 200mg 3.6 2.9 4.9 cytokines. When given intravenously, the
Aspirin 600mg/650mg 4.4 4.0 4.9 onset of action is almost immediate with the
new drugs, the mechanism of action is known
and focused, and the frequency of adverse
reactions in the short term is low. Any long-
REPORT FROM PRAGUE Interestingly, early estimates from research term adverse reactions are unknown as yet.
Clare Dunlop, Senior Chartered suggest that 7-25% of chronic pain patients
Physiotherapist have a diagnosable anxiety disorder (11% “Chronic Pain: Neuroplasticity in Limbic
Pain Management Programme social phobias, 25% specific phobias, and Structures” was a talk about how the memory
Astley Ainslie Hospital 40% PTSD). of pain could be more damaging than its’
initial experience. The central nervous system
PAIN IN EUROPE IV “Hypervigilance to Pain : An seems to have the ability to acquire and store
“Europe Against Pain, Don’t Suffer in Experimental Approach” looked at the memories of aversive events. Behavioural
Silence” differences between vigilance and responses resulting from aversive memories
hypervigilance. Vigilance is to sustain will diminish over time to become extinct, as
The fourth Congress of the European attention to weak external signals (visual or long as reinforcement of the memories is
Federation of the International Association for auditory) in a monotonous situation. absent. Long term changes in the nervous
the Study of Pain Chapters was held in Prague Hypervigilance is a perceptual habit of system may aggravate sensory discriminative
in the Czech Republic, from September 2nd scanning the body for somatic sensations. and aversive dimensions of pain, and these
until September 6th 2003. The conference Intense chronic pain causes a chronic may outlast the primary cause for the pain.
consisted of plenary lectures and a variety of interruption of attention, with no other stimuli
seminars throughout each day. I will expand to compete with it. Patients can end up in a “Psychosocial Determinants of Pain
upon a few of the sessions that I enjoyed the situation called Attentional Stuckness which Chronification” emphasised the importance
most. means that once pain is detected, it is difficult of paying attention to the complexity and
to switch attention back to other demands in dynamics of the pain experience. It has been
“Pain and Anxiety” was a plenary session the environment. Patients (especially those demonstrated in the past that several
presented via a telephone link from Canada. who catastrophise about the pain) have great psychosocial factors contribute to the
The speaker focused on presenting the difficulty disengaging from it. chronification of pain. They interact with the
differences between fear and anxiety. Fear is somatic/nociceptive dimensions and may
oriented in the present and is designed to “Pain Related Fear Amplifies Pain in modify appraisal, coping and behaviour.
protect one from immediate threat, whereas Chronic Pain Patients” was a presentation of Psychosocial factors were addressed in terms
anxiety is oriented in the future and occurs in findings from a study that found that inducing of 5 dimensions:
response to anticipated threats. Fear motivates pain anticipation (by instruction) led to 1. Physiological/disease perspective
defensive behaviours, but anxiety motivates significantly lower levels of behavioural 2. Narrative perspective
preventive behaviours. Both these responses performance and an increase in pain intensity 3. Individual dimensions
are protective, and they trigger each other in and anxiety in the experimental group. They 4. S o c i a l / a n t h r o p o l o g i c a l
a mutually reinforcing fashion. Anxiety also noticed that behavioural performance was dimensions
increases the chances that immediate threat highly correlated with the amount of fear/ 5. Behaviour
will be perceived, leading to fear. Fear forces avoidance beliefs. It was concluded that pain If clinicians take into account the whole
recognition of the stimulus (and something anticipation and fear/avoidance beliefs pain experience, the patient’s understanding
associated with it) as a threat which may/may motivate avoidance behaviour and amplify can improve, as well as the quality of the
not occur, therefore provoking anxiety. pain experience. Inducing pain anticipation therapist/patient relationship.
 “Traumatic Memories:Their Role in Pain
Chronification” Literature shows different
kinds of pain where traumatic events play a
part in maintaining pain. The influence of
traumatic experiences should not be
underestimated. The importance of a traumatic
event depends upon how subjectively the
person views it, rather than its objective
reality. It is therefore important that as
clinicians we respect the subjectivity of
trauma, as a way of helping to prevent PTSD.
CAPTION COMPETITION
The winner of last issue’s caption
competition is Dr. Colin Miller, from Glasgow
with: -
Belly dancer says “Right, so now my
radio operated TENS bra is switched on”. To
which Alan Semple thinks “Oops, she’s also
switched on my TENS underpants, I hope
nobody notices!”

“Fibromyalgia: Psychological Aspects”.

Fibromyalgia is a multidimensional syndrome
consisting of a dynamic interaction between
somatic, psychological and social factors.
Physical and psychological comorbidities can
predict emotional distress and an increase in
health seeking behaviours. Also, features of
somatisation can predict the onset of chronic
widespread pain, although there is no strict
causality relationship. The patient’s subjective
experience is important, and could be used as
a predictor of : hypervigilance to bodily If you would like to be the recipient of a
symptoms, emotional distress, and negative £20 book token then have a look at this
appraisal of life events. Difficulties include a photograph of Dr. Pete MacKenzie from
lack of specific treatment and clear aetiology. Glasgow and send in your entry to me at
Giving the diagnosis of fibromyalgia can be a colin.rae@northglasgow.scot.nhs.uk
double-edged sword. It may stigmatise the
patient, but can provide an understanding of
their situation, which in turn could lessen
uncertainty. A diagnosis may validate and
legitimise problems, but could be a source of PAIN NEWS AND GOSSIP
ambivalence.
“Attributions and Illness Narrative”. The
As mentioned previously, Anne Kelly and the two will combine to make life very hectic!
speaker in this seminar discussed how the
Ruhy Parris are to retire from Council and we Congratulations also to Sioban Calwell,
patient’s story is often neglected. Patients need
send them our sincere thanks and best wishes. winner of last year’s essay competition, who
to be listened to, particularly for them to reveal
They may hope for a quiet time off council is now the proud mother of twin boys.
important psychosocial issues, stressors,
bur an ex NBPA Chairman has recently
psychiatric comorbidities, anxiety, and/or
featured in the pages of a Sunday newspaper
depression issues. Listening well may
(a respectable one too!). Murray Carmichael
facilitate lifestyle changes and reveal specific
is to make a return visit to Cambodia, where
therapeutic needs. If a patient feels they have
he last worked in 1975 and witnessed the
not been listened to, the result may be an
horrors of the Khmer Rouge takeover. In fact,
increase in health-care seeking behaviour. The
Murray’s experiences where the basis for one
patient’s story may reveal adverse/traumatic
of the main characters in the film, “The Killing
childhood experiences, carrying the risk of
Fields”. His return visit has aroused great
personality disorders that may negatively
interest within Cambodia and I am sure the
interfere with treatment. Most fibromyalgia
trip will be a memorable one. Congratulations
patients report an overactive premorbid
to Alistair Chambers in Aberdeen on becoming
lifestyle (e.g. perfectionistic, overachieving,
both a Professor and a father again. I am sure
and/or self-sacrificing), which could be a
source of chronic stress. Many patients report
that their symptoms started after a protracted
period of physical and/or emotional
overburdening. This could suggest that the
symptoms reflect a shift within the stress
system from hyper to hypofunction, which
implies the inability of adequately responding
to new stressors. There has also been growing
evidence of disturbed pain processing and
neuroimmune dysfunction in fibromyalgia
patients.

This was a very interesting conference Drs Tom McCubbin, John Brown
and John Asbury Dr. Donny McMillan
from which I learned a great deal. I must thank
the NBPA, Lorna’s Lottery (NHS Midlothian),
and the Pain Management Programme (Astley
Ainslie Hospital) for the financial
contributions, as without them I would have
been unable to attend.

Clare Dunlop,
Senior Chartered Physiotherapist
Pain Management Programme
Astley Ainslie Hospital
Edinburgh EH9 2HL
0131-537-9128/9130
Clare.mooney@lpct.scot.nhs.uk Nicola Stuckey and Anne Kelly Dr. Ruhy Parris and Dr Donald McMillan