Almay, B. G. L., Johansson , F., von Knorring, L., Sedvall, G. & Teren ius, L. (1980).
Relationships between CSF levels of endorphins and monoamine metabolites in chronic
pain patients . Psyehopharmae.. 67. 139-142 .
Almay, B. G. L., Johansson, F., von Knorring, L., Terenius, L. & Aström , M. (1978).
Endorphins in chronic pain . I. DifTerences in CSF endorphin levels between organic and
psychogenic pain syndromes . Pain, 5, 153-162 .
Asberg, M., Thoren , P., Träskman, L., Bertilsson, L. & Ringberger, V. (1976). Serotonin
depression - A biochemical subgroup within the afTective disorders? Science, 191,
Besson, J.-M. R. (1980). Supraspinal modulation ofthe segmental transmission ofpain. In Pain
and Society, ed. Kosterlitz, H. W. & Terenius, L., pp. 161-182. Weinheim : Verlag Chemie
Fields, H. L. & Basbaum, A. I. (1978). Brainstem control of spinal pain transmission neurons .
Ann. Rev. Physiol., 40, 193-221.
Goodwin, F. K., Muscettola , J., Gold, P. W. & Wehr, F. (1978). Psychiatrie diagnosis. New
Henry, J. L. (1976). EfTects ofsubstance P on functionally identified units in cat spinal cord.
Hökfelt, T., Ljungdahl, A., Terenius , L., Eide, R. & Nilsson, G. (1977). Immunohistochemical
analysis of peptide pathways possibly related to pain and analgesia: Enkephalin and
substance P. Proe. Nat . Aead. Sei. USA. 74,3081-3085.
Hosobuchi, Y., Adams, J. E. & Linchitz, R. (1977). Pain relief by electrical stimulation of
central gray matter in humans, and its reversal by naloxone . Science, 197,183-186.
Jessel, T. M. & Iversen, L. L. (1977). Opiate analgesics inhibit substance P release from rat
trigeminal nucleus. Nature, 268, 549-551.
Johansson, F. &von Knorring, L. (1979). A double-blind controlled study ofa serotonin uptake
inhibitor (zimelidine) versus placebo in chronic pain patients . Pain , 7,69-78.
Johansson, F., von Knorring, L., Sedvall, G . & Terenius, L. (1980). Changes in endorphins and
Lamotte, C , Pert , C B. & Snyder, S. H. (1976). Opiate receptor binding in prim ate spinal cord :
distribution and changes after dorsal root section. Brain R es.. 112,407-412.
Lascelles, P. T., Evans , P. R., Merskey, H. & Sabur, M. A. (1974). Plasma corti sol in psychiatric
and neurological patients with pain . Brain, 97, 533-538 .
Levine, J. D., Gordon, N. C , Jones, R. T. & Fields , H. L. (1978). The narcotic antagonist
naloxone enhanccs clinical pain. Nature, 272,826-827.
Lombard, M. C , Nashold, B. S., Jr. & Albe-Fessard , D. (1979). DeafTerentation hypersensit ivity
in the rat after dorsal rhizotomy. A possible animal model for chronic pain, Pain, 6,
Merske y, H. & Hester, R. N. (1972). The treatment of chronic pain with psychotropic drugs.
Postgrad. m ed. J ., 48, 594-598. -
Ogren , S. O. & Holm , A.-C (1980). Test-spe ci fic efTects of the 5- HT reuptake inhibitors
alaproclate and zimelidin e on pain sensitivity and morphine analgesia. J. Ne ura/ Tran sm..
Shenkin, H. A. (1964). Th e efTect of pain on the diurnal patt ern of plasma corticoid levels.
Sjölund, B. H. & Eriksson , M. B. E. (1979). The influence ofnaloxonc on analge sia produced by
peripheral conditioning stimulation. Brain Res., 173,295-301.
Sjölund, B. H., Terenius, L. & Eriksson, M. B. E. (1977). Increased cerebrospinal fluid levels of
endorphins after electroacupuncture. ACla ph ysiol. Scand., 100,382-384.
Sternbach, R. A. (1974). Pain Patient s: Trait s and Trea tment. New York: Academic Press.
Sternbach , R. A. (1976). The need for an animal model ofchronic pain . Pain, 2,2-4.
Tamsen, A., Hart vig, P., Dahlström, 8. , Wahl ström , A. & Terenius, L. (1980). Endorphins and
on-demand pain relief. Lan cet, 1,769-770.
Terenius, L. (1978). Endogenous pept ides and analgesia. Ann . Rev. Pharmac. Toxico/.. 18,
Terenius, L. & Wahl ström , A. (1975). Morphine-like ligand for opiate receptors in human CSF.
Terenius, L. & Wahlström, A. (1979). Endorphins and clinical pain , an overview. Adv. exp.
Terenius, L., Wahlström, A. & Ägren, H. (1977). Naloxone treatment in depression: Clinical
observations and efTects on CSF endorphins and monoamine metabolites.
von Knorr ing, L. (1975). The experience ofpain in pat ient s with depres sive disorders. A clinical
and experimental study. Ume ä University M edica/ Dissertations, New Series, 2.
von Knorring, L., Almay, B. G. L., Johansson, F. & Terenius, L. (1978). Pain perception and
endorphin levels in cerebrospinal fluid. Pain, 5, 359-365.
von Knorring, L., Almay, B. G. L., Johansson, F. & Terenius, L. (1979). Endorphins in CSF of
chronic pain patients, in relation to augmenting-reducing respon se in visual averaged
evoked response . Ne uropsychobio l., 5, 322-326.
Wahlström, A. & Terenius, L. (1980). Chemical characteristics of endorphins in human
cerebrospin al fluid. FEBSLeuer, in press.
Wall , P. D., Scadding, J. W. & Tomkiewicz, M. M. (1979). T he production and prevention of
experimental anae sthesia dolorosa. Pain, 6, 175-182.
Woods, J. H. (1980). Neurochemical analysis ofcerebrospinal fluid. Neurology, 30,645--651.
Department ofPsychological Medicin e,
Many clinicians have observed that the effectiveness of analgesie drugsis not totally
predictable, especially when given to individuals suffering chronic pain . Several
reasons for this unpredictability come to mind. For exarnple , the drug selected may
be too low in potency , it may have been given in incorrect doses or the patient may
not have taken it as directed . Looking beyond these everyday explanations the
answer might lie in variations in the way drugs for pain relief are metabolised.
Clearly any of the reasons given might be correct but, in addition, there are
psychological and social factors which have a powerful influence upon the intensity
of pain and complaint behaviour associated with it which should be taken into
account when assessing a person's needs for relief, although in man y cases only scant
or ill-informed attention is given to these issues. In addition British patients are at a
disadvantage because their doctors seem reluctant to give explanations about
illnesses, their causes and their treatments, and as a result fail to relieve feelings of
anxiety and fear, perhaps actively generating such feelings at times. Failure to relieve
the tensions aroused by pain and illness actually increases the severity of pain , and
therefore of requests for pain relieving drugs. At times it leads patients to seek the
advice of other doctors and 'shopping around' for eures for chronic pain is common
in the United States. This has little to commend it because there is a definite risk that
the patient may develop more pain or other symptoms as a result of unnecessary
investigations or surgical operations.
Pain is a subjective experience which has both cognitive and affective components,
and which arises as a result of the activity of complex and , as yet, incompletely
understood mechanisms in the central nervous system. Its presence is associated with
distinctive patterns ofbehaviour, influenced by many environmental factors, which
reveal something ofthe meaning or significanceofthe pain to the individual. In view
of the complexities described it is common practice in pain centres or c1inics with a
rnulti-disciplinary staff to analyse chronic pain problems in terms of one or more
paradigms or models from each of which appropriate methods of treatment may be
derived (Table I). For example, the biological model is appropriate for understanding
and treating patients with trigeminal neuralgia, whereas atypical facial pain may be
the leading symptom of a psychological distu rbance and require quite a different
form ofanalysis. In certain problems more than one paradigm is used as in the case of
those patients who have pain which has an obvious organic basis but amongst whom
pain is 'used' to further certain emotional needs; a subject which will be discussed
Table 1 Paradigms for analysis of'pain probl ems.
Philosoph ical/Social, based upon:
Personality characteristics and pain
Personal ity traits are the hall marks of our emotional lives and they exert an influence
upon the way we behave when ill and in pain .
Anxiousness is closely link ed to th e severity of any pain we experie nce. Th e
anxi ety-prone person appears to feel pai n more often and more intensely than others
of a calmer nature. An xiety is th e pred omi nant emotional result of acute pain,
although the levels reached difTer in eac h person and in each individual fro m one
occasion to another depending upon the significance ofthe condition giving rise to
pain and the rapidity with which successful treatment is given. In oth er word s anxiety
forms the main component of th e emotiona l response to acute ph ysical distress. It
also occurs in those with chronic pain tending to reach its highest levels when new
symptoms appear, when the pat ient senses that his or her condition is worsening or
when doctors seem to have lost control ove r, or inte rest in their treatm ent. Th erefore
it follows that in the treatm ent of acute or chro nic pai n vigorous atte mpts mu st be
mad e to control an xiety using common-sense explan ations of the probl em and its
treatment and , when appropriate, techniques for inducing relaxation and calmness in
addition to the use ofanalgesic or other drug s to relieve pain.
An individual with hyste rical personalit y traits is extraverted, seeks the lirnelight,
is unable to tolerat e periods of solitude and make s shallow emotional relationships
with oth ers. He, or more often she, tends to express life's joys and sorrows vividly and
in encounte rs with others often prove emo tionally exha usting. When in pain the
person with hysterical cha racteristics exaggerates his or her feelings and this may
reach such gross proportions that even the most experienc ed c1inician has diffrcult y
in reach ing an accurate diagnosis. Doctors who encounter pat ient s with these
cha racteristics may qu ickl y experience an ger and frustration and the pat ients volatile
react ion s often lead to an abrupt end ing of'th e doctor-patient relationship.
Hypochondriasis is a very common personality trait in the general population and
is defmed as an unn ecessar y preoccupation with personal health matters.
individuals who take exerc ise in excess of their dail y needs or who have 'food fads'
linked to worries about health. It is not sur prising that family doctors have to deal
with hypo chondriacal patients more often than alm ost any other types and pain is
probabl y th e most common presenting complaint amongst them. Th erefore , great
care must be taken, because although most of the visits of hypochondriacal pat ient s
are centred upon tr ivial ph ysical disord ers, occasionally they signify something more
PSYCHOLOGICAL ASPECTS OF PAIN 347
serious. A person presenting for the first time with hypochondriacal syrnptoms may
be suffering from one of several mental disorders, for example an anxiety neurosis,
depressive illness or schizophrenia.
Individuals with a gloomy and pessimistic nature and a low level oftolerance for
physical and emotional stress tend to find pain difficult to bear. Depressive reactions
are often accompanied by pain, especially in the head, ehest and abdomen. Amongst
those who have been bereaved, a special form of depressive reaction occurs and the
bereaved person may experience pain closely resembling that of the recently dead
relative or friend, especially ifthere were unresolved interpersonal conflicts between
the two leaving feelings of guilt, anger or both in the survivor. Thus, it is clear that
personality traits have a marked influence upon pain experience and the behaviour
'Psychosomatic' disorders and pain
Pain due to physical causes is modified by emotion and, converscly, painful physical
conditions are sometimes precipitated and/or maintained by altered emotions. The
latter are often known as psychosomatic illnesses, although the exact meaning ofthis
term is the subject of continuous debate. Migraine is an example of this form of
disorder as are peptic ulceration, ulcerative colitis and the irritable bowel syndrome.
All are painful to a variable extent and their pre sence is clearly related to emotional
factors in many patients. The personality trait which seems to be common to many of
the sufferers ofpainful psychosomatic illnesses is a difficulty in expressing emotional
In more general terms, when responding to stresses in the horne or at work, and to
conflict over personal failures and disappointments, each of us responds differently.
The effect is 'psychosornatic' in the sense that the acute emotional reaction brings
physical symptoms with it. Pain is a common symptom and at times the combination
of symptoms may give rise to the belief that the sufferer has a physical illness. For
example, acute anxiety may be accompanied by ehest pain, pallor, sweating and
faintness, leading to the view that he or she is suffering from an acute myocardial
infa rction. In less acute or chronic reactive emotional states the ph ysiological
responses described are absent but, nevertheless, the person has pain and this is often
regarded as an indication of organic disease. In some cases this leads to aseries of
fruitless investigations, but if the doctor suspects that emotions pla ya major role in
the causation ofthe pain he is confronted by two possible diagnoses. The patient may
have an underlying depressive illness whi ch will respond to conventional treatment
with antidepressant drugs, or the pain may be a presenting feature of a longstanding
disorder ofpersonality development.
Approximately half of all patients attending psychiatric clinics have pain and
amongst them those with depressive illnesses are common. The pain they suffer is
experienced chiefly in the face or about the head and for rea sons that are not c1early
understood they occur at the sites of previous injuries or surgical operations and
affiict th e left halfofthe body more often than the right side . Pain at sites ofprevious
trauma draws atte ntion to the possibility of a recurrent ph ysical problem and this
often causes diagnostic difficulties, especially when mood changes seem mild in
comparison with the apparent severity of pain. In this situation complaints of pain
are regarded as secondary rather than primary events. However. as with the more
obviously depressed patients, treatment with antidepressant drugs brings pain relief.
In the light of recent work on pain modulating systems in the central nervous system
the primacy of mood change as a cause of pain may have to be revised because both
pain and depression may weil be symptorns of a disturbance of modulating
mechanisms common to mood and the control of pain experiences. There is some
support for this view from recent studies of opioid peptide levels in the cerebrospinal
fluid of depressed patients and those in pain, and from clinical evidence based upon
the effects of tricyclic and monoamine oxidase inhibitor antidepressants which alter
levels ofneurotransmitters in pain and mood control systems .
Chronic pain as part of a disorder of personality development
Apart from its value as an indicator oftissue injury and its occurrence in neurotic and
psychotic emotional disorders pain may have certain 'uses'. In other words the
presence of pain helps some individuals to cope with difficulties in life that would be
almost intolerable otherwise. For example, pain may appear at times when a person
wishes to avoid responsibilities in the horne or at work, when he or she wishes to
exert control over others, feels guilt about misdeeds, or seeks comfort and support
from relatives or friends . The hall mark of 'Pain Prone People', as they have been
calied, is their apparent unawareness of the relationship between the appearance of
pain and background emotional problems. They strongly resist attempts to explain
their physical experiences in terms of emotional causes protesting that mental
disturbances are secondary events. Furthermore, family members are often involved
in the patient's problerns and mayaiso resist, or even obstruct, attempts to change the
status qua. Pain patients of this type , though small in number, have a number of
characteristics in common. Most are women and have had pain for several years. The
time of onset of pain is seldom remembered clearly and several specialists will have
been consulted and carried out a wide range of tests most of which will have proved
negative or, at best, doubtfully positive. In about half surgical operations will have
been performed (unsuccessfully), and all will have been given a very wide range of
medicines for pain relief but with very limited success. Psychological testing reveals
marked hypochondriasis and difficulty in expressing angry and hostile feelings
openly. Clearly, the patients' endless search for a physical cause for pain and the
tenacity with which they hold their views about the need to find its source in some
disturbance of body function make them resist referral to a psychiatrist. Those who
reach psychiatrie clinics are very difficult to manage. Most have found conventional
physical methods for pain relief useless, although a minority become habituated to
analgesics and /or minor tranquillisers. They are not suitable candidates for
individual psychotherapy in view of their very strong resistance to any attempt to
explore their personal mental lives. However, limited success has been gained using
group psychotherapy where, under the influence of fellow sufferers, the individual
patient may achieve goals or targets set by the group; for example, in terms of
increased hours of activity each day or reduced dependency upon other family
members. The greatest degree of success has been gained by the use of behaviour
modification techniques which depend upon altering 'pain behaviours' by rewarding
desirable activities and attitudes and ignoring those which are undesirable. For
example, the sufferer may spend several hours each day in bed, although potentially
capable ofmuch more activity. A detailed work plan is designed by the therapist and
the patient is given periods of rest, but only in return for a specified amount of
activity. He or she is given eonsiderable encouragement and , if successful,
commended for the efforts made . This form of therapy is most productive when
carried out at special centres and, initially at least, on a resident basis. Those
responsible for the organisation of care often use combinations of behavioural
techniques, groups and physical methods oftreatment.
Most of those who sufTer from acute pain gain relief quite quickly by means of
physical treatment but it is clear that individual emotional characteristics influence
the nature of sufTering and its mode of presentation to others. Many of those who
have to bear chronic pain also respond satisfactorily to physical methods of
treatment but, in addition, behave difTerently in ways determined by personal and
soci al factors. In addition they are also liable to experience emotional difficulties as a
result of prolonged sufTering and may need psychiatrie or psychological help to gain
satisfactory relieffrom sufTering. In neurotic and psychotic illnesses pain is a possible
symptom which responds to conventional psychiatrie methods of treatment. Finally
there is a small group ofpeople for whom being in pain seems to be a necessary part
oflife if'psychic equilibrium is to be maintained. They are very resistant to almost all
forms of treatment except behavioural management techniques which bring modest
Bond, M. R. (1979). Pain, lts Nature, Analysis and Treatment. Edinburgh, London: Churchill
Fordyce, W. E. (1976). Behaviour Methods in Chronic Pain and IIIness. St. Louis: C. V. Mosby
The Psychology ofPain. (1978). Ed. Sternbach, R. A. New York: Raven Press.
Lilly Lab oratoryfo r Clinical Research,
The Departm ents ofPharmacology, Medicine and Psychiatry,
Indiana University School ofMedic ine,
Indianapolis, Indiana 46202, USA
Medicinals derived from plants and other natural products have been utilized for
many centuries. In fact , many drugs currently in the ph ysician 's armamentarium are
ofbotanical origin (Table I). Marihuana is the common name given to the leaves and
flower ing tops obtained from the plant Cannabis sativa. Cannabis has been utilized
for medi cinal purposes for nearl y 5,000 years. The Chinese Emperor Shen Nung
published a monograph in 3,000 BC describing cannabis usage in the treatment of
several disorders, including migraine, asthma and gynaecological problems. An
extensive treatise on the use of cannabis for various medical conditions was
Although cannabis and its derivatives are not currently sanctioned for medicinal
purposes, various pharmaceutical preparations ofthe drug were official in the United
States Pharmacopoeia from 1850 until 1942. The medicinal use of cannabis was
terminated in 1937 with enactment ofthe Marihuana Tax Law . Recent evidence for
the potential therapeutic usefulness ofcannabis-derived compounds has resulted in a
re-e valuation ofthe role ofcannabis in medicine.
Cannabis sativa contains a variety of chemical constituents, including those with
the unique cannabinoid structure. More than 20 cannabinoids have been obtained
from the plant and their structures identified. .6,9- tetrahydrocanna binol (.6,9-THC)
(Figure 1), one such compound, was isolated by Gaoni & Mechoulam (1964) and
was reported to be the major pharmacologically acti ve constituent of cannabis.
Although many years have elapsed since this initial cla im by Gaoni & Mechoulam
(1964), it appears that the major acti ve constituent in cannabis is, in fact,
Table1 Drugsofbotanical origin
Erythroxylon coca Pilocarpusjaborandi
seV ERAL "'''TURALLV OCCUfUIING CANNA81NOIDS
SEVERAL SY N THET IC CANNAB I NOI DS
Figure 1 Structure ofseveral naturally occurringcannabinoidsand severalsynthetic
Animal studies and human experiences have shown that cannabis has a large
therapeutic index, that is, pharmacological effects occur at doses which produce little
toxicity. The clinical pharmacological effects of single doses of 6 9- THC are :
tachycardia with minimal effects on Iying or standing blood pressure; a psychological
effects have been shown to be dose related.
Many congeners of 6 9_ THC have been synthesized over the past generation
(Figure I). During this time, several of these compounds have been administered to
healthy volunteers for clinical pharmacological evaluation and, to a lesser extent, to
patients in therapeutic trials. lt is clear that differences exist between the clinical
MARIH UANA A NO RELATEO ORUGS 355
pharmacological efTects of t, 9_THC and those of the synthetic cannabinoids such as
nabilone. For example, nabilone produces only a minimal euphoria at doses which
produce significant pharmacological activity with respect to its potential therapeutic
usefulness (Herman, Jones, Dean, Leigh, Dorr, Moon & Salmon, 1977), whereas a
greater degree of euphoria occurs with t,9-THC.Furthermore, nabilone, even at doses
which produce marked pharmacological effects, does not produce any significant
elevation in heart rate (Lemberger & Rowe, 1975) in contrast to t, 9-T HC
(Lemberger, Martz, Rodda, Forney & Rowe, 1973)(Figure 2 and Table 2).
Table2 Clinical pharmacologyofseveralcannabinoids after oral or intravenous
Effect t, 9THC t,9THC DMHP O.5mg 2mg
Tachycardia ++ + + + + ++ + + 0
Psychological high + + ++ + 0 + ± Dry mouth +++ ++ + + ++ + ++ +
Sedative, relaxant + + + + + + ± +++ + + +
Figure2 Mean change in heart rate (comparedto placebo)after three oral doses ofnabilone .
analogues which may be useful therapeutic agents and which may be ofvalue in the
treatrnent, eure or prevention of diseases. Extensive research has been und ertaken
during the last decade to study the efTects of marihuana, t,9-T HC and synthetic
cannabinoids in an imals and man to determine their usefulness as therapeutic agents
in a variety ofpharmacological areas.
Cannabinoids have been evaluated as analgesie agents. The results ofthese studies
appear to be controversial since some studies demonstrate that analgesie activity
occurs with t,9-THC (Noyes, Brunk, Baram & Canter, 1976) as weil as with synthetic
cannabinoids (Staquet, Gantt & Mach in , 197 8; Dren , 197 6; Stark & Archer, 1975). In
contrast, others ha ve reported a lack of analgesie efTects from th ese compo unds (Hili ,
Sch win , G oodwin & Powell , 1974; Jochimsen , Lawton, Versteeg & Noyes, 1978;
Raft, Gregg, Ghia & Harris, 1977).
Ca nnabinoi ds ha ve also been evaluated in hyperten sion . Stu dies in spontaneously
hypertensive rats ha ve shown th at 6 9_THC lowers blood pr essure (Birmi ngha m,
1973; Na has, Schwartz, Adamec & Manger, 1973; Lewis, Neel, Brown & Forney,
Comments
Post a Comment
اكتب تعليق حول الموضوع