Immediate and long-term phantom limb pain in amputees: Incidence, clinical characteristics and relationship to pre-amputation limb pain

Pain, 21 (1985) 267-278 Elsevier

267

PA1 00724

Immediate and Long-Term Phantom Limb Pain in Amputees: Incidence, Clinical Characteristics and Relationship to Pre-Amputation Limb Pain Troels S. Jensen *,’ , Berrge Krebs **, Jplrn Nielsen ** and Peter Rasmussen *** Departments of + Neurology, ** Orthopedic Surgery and *** Neurosurgery Aarhus University Hospital, DK - 8000 Aarhus C (Denmark) (Received

4 July 1984, accepted

22 October

1984)

Summary

In a prospective study 58 patients undergoing limb amputation were interviewed the day before operation about their pre-amputation limb pain and 8 days, 6 months and 2 years after limb loss about their stump and phantom limb pain. All but one patient had experienced pain in the limb prior to amputation. Pre-amputation limb pain lasted less than 1 month in 25% of patients and more than 1 month in the remaining 75% of patients. At the first examination the day before amputation 29% had no limb pain. The incidence of phantom pain 8 days, 6 months and 2 years after amputation was 72, 65 and 59%, respectively. Within the first half year after limb loss phantom pain was significantly more frequent in patients with long-lasting pre-amputation limb pain and in patients with pain in the limb immediately prior to amputation. Phantom pain and pre-amputation pain were similar in both localization and character in 36% of patients immediately after amputation but in only 10% of patients later in the course. Both the localization and character of phantom pain changed within the first half year; no further change occurred later in the course. The incidence of stump pain 8 days, 6 months and 2 years after limb loss was 57, 22 and 21%, respectively. It is suggested that preoperative limb pain plays a role in phantom pain immediately after amputation, but probably not in late persistent phantom pain.

’ Please address correspondence to: Medicine, University of Copenhagen, 0304-3959/85/$03.30

Dr. Troels S. Jensen, Department of Neurology, Gentofte Hospital, DK-2900 Hellerup, Denmark.

0 1985 Elsevier Science Publishers

B.V. (Biomedical

Division)

Faculty

of

26X

Introduction Immediately after amputation, patients often have a phantom limb. which can be painful or painless. Carlen et al. [4] found that 67%’ of young soldiers having traumatic amputation had pain in the phantom during the first months. Recently we reported a similar figure in a group of mainly non-traumatic amputees followed during the first half year after limb amputation [ll]. The above incidence of phantom pain is considerably higher than the usual reported incidence of severe chronic phantom pain, which is stated to be within the range of 0.5.~10%; of amputees [1,3,5-8,101. These observations may therefore suggest that phantom pain decreases in intensity and frequency after the first 6 months have elapsed. The mechanisms underlying phantom pain are not generally agreed upon. Peripheral, spinal cord and supraspinal mechanisms have been proposed [10,14,22,23]. Some authors have suggested that phantom pain is a reminiscence of pain existing in the limb prior to amputation. leading to the hypothesis that phantom pain could be due to establishment of a nociceptive engram in some cerebral structures [14,15]. However, since no study has been carried out in which pre-amputation limb pain has been recorded before amputation, there is no substantial evidence to support this hypothesis. In the present study we investigated (1) the clinical picture of pre-amputation pain in patients scheduled for limb amputation and (2) the possible relationship between pre-amputation limb pain and later occurring phantom pain.

Materials and Methods This is a prospective study of 58 patients who underwent a limb amputation at one of three hospitals in the Aarhus area from April 1980 to March 1982. The basic clinical characteristics of these patients and the procedure used have been described previously [9,11]. Briefly, patients scheduled for a limb amputation were interviewed by means of a standard questionnaire and examined the day before amputation, 8 days, 6 months and 2 years after surgery. They were questioned about pre-amputation limb pain at the first interview and about phantom limb pain and stump pain at the 3 later examinations. The following patients were excluded from the study: (1) Acute traumatic limb lesions requiring amputation; (2) ipsilateral re-amputation; (3) patients who at the interview presented a clinical dementia of such degree that they could not answer the questionnaire reliably. Phantom pain was classified as painful sensations referred to the lost part and stump pain was defined as painful sensations localized to the stump. So that the temporal course of phantom pain could be studied, no therapeutic trial was carried out during the period of study. However, patients having phantom or stump pain were allowed to take analgetics for their pain. For descriptive reasons, in the following section the distribution of pain has been divided into 3 categories: (1) entire limb pain: pain in the whole limb; (2) distal limb pain: pain limited to

269

peripheral parts of the limb (e.g., digits, foot or hand); and (3) proximal and distal limb pain: pain in peripheral parts of the limb and near the stump end with no pain in intermediate parts (e.g., knee, calf, etc.). Statistical analysis was carried out using x2 and Fischer’s exact test. P values less than 0.05 were considered to be statistically significant.

Results

Fifty-eight patients, aged 24-91 years (mean 69.8 years) entered the study. There were 56 lower limb amputees (32 below knee, 23 above knee, 1 through the knee joint) and 2 upper limb amputees (1 below elbow and 1 above elbow). The main reason for amputation was occlusive arterial disease in 51 patients, 18 of which had associated diabetes mellitus. In the remaining patients the reason for amputation was neoplasm in 5, osteomyelitis in 1 and a brachial plexus avulsion in 1. The clinical characteristics of the patients at the 3 postoperative assessments are shown in Table I. Seven patients died within the first 6 months after amputation, and 2 years after limb loss 24 patients (41%) were dead. As can be seen in Table I, neither diabetes mellitus, nor previous contralateral amputation or proximal amputation was associated with a poorer survival rate as compared to non-diabetics, no previous amputation or distal amputation, respectively. Pre-amputation limb pain

Pain in the limb prior to amputation was experienced by 57 patients (98%). Table II shows the localization, duration and frequency of reported pre-amputation pain. Half of the patients had pain only in the distal part of the limb, while the remaining patients had either pain in the entire limb or in its proximal and distal parts. One quarter of the patients reported pain lasting less than 1 month, while the rest had had pain for several months or years. Nearly half of the patients were in constant pain, while the rest had intermittent limb pain with days or weeks interval. Forty patients (69%) had received analgetics regularly because of pre-amputation pain and

TABLE

I

CLINICAL CHARACTERISTICS AMPUTATION 8 days

Total Sex Proximal amputation Previous amputation Diabetes mellitus

58 29 F 25 17 18

OF AMPUTEES

AT THE

3 EXAMINATIONS

6 months (mean: 5.6 months)

2 years (mean: 24.7 months)

51 27 F 21 13 16

34 17 F 15 5 8

AFTER

df=2 x2

P

0.11 0.08 2.51 0.74

N.S. N.S. N.S. N.S.

LIMB

270 TABLE

II

LOCALIZATION, DURATION AND FREQUENCY OF PRE-AMPUTATION OUT OF 58 PATIENTS UNDERGOING LIMB AMPUTATION Pre-amputation

pain

N

%

14 14 29

25 25 51

14 27 16

25 47 28

27 20 10

47 35 18

LIMB PAIN

IN 57

Localization Entire limb Proximal and distal Distal Duration < 1 month I ---6 months > 6 months Frequency Constant daily Intermittent daily Days interval

27 of these (47%) were receiving narcotics to relieve their pain. The day before operation 17 patients (29%) had no limb pain, while 41 patients (71%) still had some pain. The character of pre-amputation limb pain varied considerably among patients, the most frequent character being a knifelike or sticking pain (Table III). Phuntom pain Phantom pain was a frequent

TABLE

complaint

at the 3 interviews

after limb amputa-

III

PAINFUL SENSATIONS IN THE LIMB EXPERIENCED OF 58 PATIENTS UNDERGOING LIMB AMPUTATION

PRIOR

TO AMPUTATION

Pain character

N

w

Knifelike Sticking Shooting Pricking Burning Squeezing Throbbing Pressing Cramplike Sawing Dull Freezing Crushing Other

20 1x 3 11 13 12 11 8 0 0 4 2

35 32 5 19 23 21 19 14 0 0 7 4 2 5

I 3

IN 57 OUT

271

tion. The incidence of phanton pain 8 days, 6 months and 2 years after amputation was 72, 65 and 598, respectively. Phantom pain was usually an exaggeration of non-painful phantom limb sensations [12]. The incidence of non-painful phantom limb at the 3 assessments after amputation was 84, 90 and 71%, respectively. Six months after amputation 1 of 5 patients without non-painful phantom limb had phantom pain, and 2 years after amputation, 4 out of 10 patients without non-painful phantom had phantom pain. While the incidence of phantom pain did not decline significantly (x2 = 1.88, u”= 2, N.S.) both the duration (x2 = 10.45, df = 4, P -C0.05) and the frequency (x2 = 20.56, df = 4, P < 0.001) of phantom pain attacks decreased during the two follow-up periods (Fig. 1). This decrease in duration and frequency of phantom pain attacks occurred within the first 6 months after amputation, while no further decrease in duration (x2 = 1.45, df = 2, N.S.) or frequency (x2 = 1.22, df = 2, N.S.) was seen during the last 1.5 year follow-up period. During the first 6 months after amputation, 17 patients reported no decrease in the phantom pain; 12 of these patients were alive 2 years after amputation and all continued to have phantom pain. None of the patients were in constant pain at the latest examination, but 7 patients (21%) had attacks of phantom pain daily. Sixteen patients reported decrease in phantom pain during the first 6 months; seven of these

IOO-

,.-n

$l-!hzla DAILY

DAYS WEEKS INTERVAL

50 -

o-

dzI SEC

l-5 MIN

.I0 MIN

Fig. 1. The frequency (top) and the duration (bottom) of phantom pain attacks in amputees 8 days (open bars), 6 months (hatched bars) and 2 years (black bars) after limb amputation. The bars represent percentages of patients with phantom pain 8 days (N = 42), 6 months (N = 33) and 2 years (N = 20) after limb loss.

272

were alive 2 years phantom pain.

after

amputation

and

only

four of these continued

to have

Localization of phantom pain Fig. 2 shows the localization of phantom pain immediately after amputation, 6 months and 2 years later. Immediately after surgery, phantom pain was localized distally in 50% of the patients and proximally in the other 50%. At the two latest examinations phantom pain was mainly localized in distal parts of the limb. This difference is significant (x2 = 22.65, df = 4, P < 0.001). The distribution of phantom pain did not change notably from the 6 month examination to the latest follow-up 2 years after amputation. Table IV shows the distribution of the most prominent phantom pains at the 3 examinations after limb amputation. As can be seen, later in the course the most prominent localizations of phantom pain were in distal parts of the limb. Character of phantom pain Table V shows the pain characteristics reported by amputees at the 3 assessments after limb loss. Patients were asked which of 14 pain types listed in Table V best fitted with the one experienced. As previously noted [ll] pain characteristics varied considerably. Most of the patients reported two or several types of pain. Knifelike or sticking types of pain were most common immediately after amputation, while later phantom pain usually became burning or squeezing in character. Attacks of phantom pain could be provoked by various environmental stimuli such as emotional distress, urination, stump pressure, cough or other factors in approximately 50% of patients at the 3 examinations after amputation. Relief of phantom pain Various factors such as rest, heat, a firm pressure applied to the stump, use of prosthesis and distraction relieved phantom pain attacks in 30-50% of amputees at

PROXIMAL DlSiAL

iI DISTAL

Fig. 2. Percentage of amputees with phantom pain involving the entire limb, proximal and distal parts and only distal parts of the limb 8 days. 6 months and 2 years after limb amputation. See Fig. I for further details.

273 TABLE

IV

LOCALIZATION OF MOST PROMINENT PAINFUL AMPUTEES 8 DAYS, 6 MONTHS AND 2 YEARS AFTER Figures

are presented

as percentages

Localization

of patients

Phantom

with phantom

pain at each postoperative

IN

examination.

pain

8 days Toes/fingers Forefoot/hand Ankle/wrist Forefoot + toes/ forehand + fingers Ankle + toes/ wrist + toes Whole foot/hand Lower leg/arm Whole limb Other

PHANTOM LfMB SENSATIONS LIMB AMPUTATION

(N = 42)

6 months (N = 33)

2 years (N = 20)

17 5 2

39 3 0

35 15 5

12

6

15

5 19 19 17 5

15 18 12 3 3

5 25 0 0 0

the 3 follow-up assessments. Two years after amputation 8 patients with phantom pain received regular treatment with analgetics (narcotics in 3 and non-narcotics in 5 patients) to relieve their pains. Prosthesis was used daily by 24 patients (71%) at the latest examination, while 10 patients (29%) did not use their prostheses. There was no significant difference of

TABLE

V

CHARACTER OF PHANTOM PAIN IN AMPUTEES 2 YEARS (N = 20) AFTER LIMB AMPUTATION Data are presented

as percentages

of patients

8 DAYS (N = 42) 6 MONTHS

with phantom

pain at each postoperative

Pain character

8 days

6 months

2 years

Knifelike

55

27

Sticking Shooting Pricking Burning Squeezing Throbbing Pressing Cramplike Sawing Dull Freezing Crushing Other

36 14 14 14 10 7 I 5 5 5 0 0 7

9 9 6 45 52 12 0 3 3 3 6 6 6

20 10 0 5 6.5 30 5 0 0 0 5 0 15 0

(N = 33) AND

examination.

274

prosthetic use between patients with phantom pain (60%) and patients without phantom pain (86%). Phantom pain was unrelated to use of prosthesis in 6 patients. In the remaining 5 patients prosthetic use relieved and worsened phantom limb pain in 2 and 4 patients, respectively. Amputees found that the worsening effect of prosthesis on phantom pain was due to a ma1 fit of the prosthesis. Similarity

between pre-amputation

pain and phantom pain

In order to study the possible relationship between pre-amputation pain and phantom pain, the most prominent distribution and the types of pre-amputation and phantom limb pain (cf., Table IV) were compared. As can be seen in Fig. 3 the localization of phantom pain was similar in 74% of patients 8 days after amputation, while the distribution of pre-amputation pain and phantom pain at the 6 month and 2 year follow-up examinations was similar in only 45% of patients. This difference is significant (x2 = 7.82, df= 2, P < 0.05). Eight days after amputation the character of phantom pain was similar to the pre-amputation pain experienced by these patients in 53% of cases. Six months and 2 years after amputation the corresponding figures were 30% and 35%, respectively. There was no significant difference between patients with a similar or different type of pain at the 3 examinations after amputation when compared to the pain type reported prior to amputation (x2 = 4.10, df= 2, N.S.). If one looks at patients who had both a similar localization and character of pre-amputation and phantom limb pain then this was seen in 36% of patients 8 days after amputation, but in only 10% of patients 6 months and 2 years after limb loss (x2 = 9.74, df = 2, P < 0.01). Table VI shows the influence of various factors for the subsequent development and persistence of phantom pain after amputation. As can be seen 6 months and 2 years after amputation, phantom pain was neither related to sex, side, level of amputation, previous amputation nor to co-existing diabetes mellitus. On the other hand, 6 months after amputation, phantom pain was significantly more frequent in those patients who had had long-lasting pre-amputation pain (i.e., pain > 1 month) than in the patients who had had short-lasting pre-amputation pain (i.e., pain < 1

I

II LOCALIZATION

III

0

SIMILAR

q

CHANGED

I

II

Ill

CHARACTER

Fig. 3. Percentages of patients in which the most prominent localization (left) and character (right) of phantom pain 8 days (I), 6 months (II) and 2 years (III) after limb amputation were similar (open bars) or differed (hatched bars) from pre-amputation pain.

215

month). In addition, 6 months after amputation phantom pain was significantly more frequent in patients who had limb pain the day before amputation compared to patients who had no limb pain immediately before amputation. Two years after amputation, neither the duration of pre-amputation pain nor the relief of limb pain immediately prior to amputation was correlated with the persistence of late phantom pain. The intensity of pre-amputation limb pain was not recorded in the present study. However, given that regular treatment with narcotics prior to amputation reflects severe pre-amputation pain, there was a trend towards a higher frequency of persistent phantom pain in patients with severe pre-amputation pain (requiring narcotics) than in patients with less severe pre-amputation pain (not requiring narcotics). Thus, 6 months after amputation 55% with phantom pain had previously received narcotics, while only 28% with no phantom pain had previously received narcotics for their pre-amputation pain. The corresponding figures 2 years after amputation were 45% and 228, respectively. Stump pain

Pain in the stump was a frequent complaint immediately after amputation and reported by 57% of amputees. Six months and 2 years after limb loss stump pain was reported by 22% and 21% of patients, respectively. As shown in Table VI, 2 years after amputation phantom pain was significantly more frequent in patients with stump pain than in amputees without stump pain. While all patients with stump pain at the last follow-up examination had areas of hyperpathia in the stump end, obvious stump pathology was only found in 2 patients (neuromas). Stump pain was either of a pressing, throbbing, burning or squeezing type at the two latest examinations. TABLE VI CLINICAL CHARACTERISTICS OF AMPUTEES RELATED TO EITHER PHANTOM PAIN OR NO PHANTOM PAIN 6 MONTHS AND 2 YEARS AFTER LIMB AMPUTATION 2 years

6 months Pain (N = 33)

Females Left-sided amputation Proximal amputation Stump pain Previous amputation Diabetes meIIitus Pre-amputation pain < 1 month No pre-amputation pain the day before amputation

No pain (N = 18)

P

Pain (N = 20)

No pain (N = 14)

P

18

9

N.S.

11

6

N.S.

15 20 7 9 8

11 6 4 4 8

N.S. N.S. N.S. N.S. N.S.

I 10 1 2 3

I 6 0 3 5

N.S. N.S. < 0.05 N.S. N.S.

5

8

< 0.05

3

I

N.S.

4

11

< 0.01

3

7

N.S.

216

Discussion

As previously reported 19,111, phantom limb pain is observed in appr~ximateI~ two-thirds of patients within the first half year after amputation. Even 2 years after amputation, 60% of patients continue to have significant phantom pain. Neither age nor the cause of amputation seems to be related to the high rate of phantom pain. Thus the incidence of phantom pain in the present series of mainly old people with peripheral vascular disease is close to the reported rate in young soidiers with traumatic amputations (41. It is unlikely that the relatively short time-span between the amputation and the clinical follow-up accounts for the high rate of phantom pain found in our study. Our recent observations show that even 7 years after limb amputation in a population similar to the present, 60% of amputees continue to have phantom pain 1131. Moreover, Sherman et al. [20,21] found that phantom pain occurred in more than 50-85516of amputated American veterans several years after limb loss. The incidence of phantom pain reported in the present study and in those by Sherman et al. is considerably higher than the usual expected rate of phantom pain (see Introduction). Although several factors may account for this discrepancy between studies, we believe that differences in method used could be one explanation. The present population and the ones studied by Sherman et al. [20,21] did not consist of patients seeking treatment to relieve their phantom pain. When the incidence of phantom pain is based in patients seeking treatment for pain, both this and previous studies show that the rate of phantom pain decreases. In our study, 31% and 21% of patients were treated for their phantom pain 6 months and 2 years after amputation, respectively. In another study covering more than 2500 amputees, 78% had phantom pain but oniy 19% were offered treatment for their phantom pain [21]. While the present study suggests that phantom pain is a more common phenomenon than is usually thought it should be noted that phantom pain varied considerably and only 20% of patients reported daily attacks of phantom pain 2 years after amputation (cf., Fig. 1). With regard to the mechanisms underlying phantom pain, some authors have emphasized peripheral and spinal cord mechanisms as the main source for the pain, while others have pointed to a cerebral origin. The notion that phantom pain may be a reactivation of a nociceptive engram established in some cerebral structures prior to amputation is supported by a few case reports [2,5,16,19]. However, this study is the first we are aware of in which the possible influence of pre-amputation limb pain (as recorded prior to ~putation) had been systematically compared to the phantom pain (as recorded at different intervals after amputation). The present observation that phantom pain was similar in both localization and character as compared to the pre-amputation pain in 36% of patients immediately after amputation, but in only 10% of patients later in the course, suggests that phantom pain immediately after amputation in some patients may represent surviving pre-amputation pain. This notion is also supported by the finding that the incidence of phantom pain is significantly lower in patients with short-lasting pre-amputation pain and in patients who did not have pain in the limb the day before amputation. However, the fact that

277

both the type and distribution of phantom pain differed from pre-amputation pain in more than 60% of patients also indicates that reactivation of previous experienced pre-amputation pain cannot be the only factor responsible for phantom pain. Moreover, the long-term phantom pain was neither related to the duration of pre-amputation pain nor to the presence of pain in the limb immediately prior to amputation. These observations therefore raise the question what other mechanisms could be responsible for the phantom pain. While phantom pain was not related to sex, side or level of amputation, late persistent pain was significantly more frequent in patients with stump pain than in patients without stump pain. Aithough definite stump pathology only was found in few patients with stump pain, areas of stump hyperpathia were present in all. This observation suggests that peripheral and/or spinal cord mechanisms may also play a role in the development and persistence of phantom pain [2,4]. A detailed and systematic analysis of the sensory properties of the stump, which was not undertaken in the present study, might give further information about the role played by peripheral/spinal cord mechanisms in phantom pain. Phantom pain changed considerably in location, character, frequency and duration within the first half year after amputation. In the typical case, phantom pain changed from a mainly exteroceptive-like pain (knifelike or sticking), localized in the entire limb or at least involving proximal parts of the lost limb, to a mainly proprioceptive type of pain (burning or squeezing) localized in the distal parts of the amputated limb. Importantly, these clinical characteristics of phantom pain did not change notably after the first 6 months had passed. It is well known that a series of anatomical, biochemical and physiological changes occur in cut peripheral nerves and in the spinal cord within the first weeks and months after experimental deafferentation in animals [for review see 231. For example, experimental studies have shown that outgrowing sprouts from sectioned peripheral nerves exhibit spontaneous activity, increased sensitivity to mechanical stimuli and to various chemical agents such as a-adrenergic substances [24]. It is for obvious reasons hazardous to draw any conclusions from such experimental findings in animals to the complex phantom limb phenomena observed in humans. However, it is tempting to speculate that the clear change in clinical pattern of phantom limb pain observed within the first 6 months of amputation may reflect dynamic changes seen in the cut peripheral nerves and in the spinal cord after experimental deafferentation in animals. The increased sensitivity of sprouts from cut peripheral nerves to noradrenaline and adrenaline [24] may in part explain why adrenergic influenced emotional states such as stress or anxiety occasionally provoke attacks of phantom limb pain in humans [ll].

Acknowledgements

We are grateful to the staffs of the Orthopedic Surgical Departments at Aarhus Amtssygehus, Aarhus Kommunehospital and Orthopedic Hospital for their help and cooperation during the 2 year study period.

27X

This study was supported in part by the Foundation in Neurology.

for Experimental Research

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