Staffan Arnér

Breakthrough pain in malignant and non-malignant diseases: a review of prevalence, characteristics and mechanisms.

Breakthrough pain or transient worsening of pain in patients with an ongoing steady pain is a well known feature in cancer pain patients, but it is also seen in non‐malignant pain conditions with involvement of nerves, muscles, bones or viscera. Continuous and intermittent pain seems to be a general feature of these different pain conditions, and this raises the possibility of one or several common mechanisms underlying breakthrough pain in malignant and non‐malignant disorders. Although the mechanisms of spontaneous ongoing pain and intermittent flares of pain (BTP) may be difficult to separate, we suggest that peripheral and/or central sensitization (hyperexcitability) may play a major role in many causes of BTP. Mechanical stimuli (e.g. micro‐fractures) changes in chemical environments and release of tumour growth factors may initiate sensitization both peripherally and centrally. It is suggested that sensitization could be the common denominator of BTP in malignant and non‐malignant pain.

The safety and efficacy of intrathecal adenosine in patients with chronic neuropathic pain

UNLABELLED: Adenosine and adenosine analogs decrease pain-like behavior in animal models of both acute nociceptive and neuropathic pain via adenosine receptor activation at spinal and/or supraspinal levels. This open study is the first in a series of intrathecal (IT) adenosine administration studied for the evaluation of efficacy and side effects in 14 patients. All had chronic neuropathic pain with tactile hyperalgesia and/or allodynia primarily of traumatic origin. The effects of IT adenosine (500 microg [n = 9] or 1000 microg [n = 5]) were evaluated. Approximate areas of tactile pain were mapped. Spontaneous and evoked pain (visual analog scale score 0-100) and tactile pain thresholds were assessed before and 60 min after injection. The injection caused transient pain (<60 min) in the lumbar region in five patients. There were no other side effects. Spontaneous and evoked pain was reduced (median score from 65 to 24 [P<0.01] and from 71 to 12 [P<0.01], respectively) in parallel with increased tactile pain thresholds in allodynic areas. Areas of tactile hyperalgesia/allodynia were reduced (median reduction 90%; P<0.001). Twelve patients experienced pain relief (median 24 h). We conclude that IT adenosine transiently causes lumbar pain in a subgroup of patients and may reduce various aspects of chronic neuropathic pain. IMPLICATIONS: This is the first series of patients with chronic neuropathic pain in which tolerability to spinal adenosine administration has been evaluated. A subset of patients reported transient low back pain as the only side effect. Spontaneous and evoked pain intensity decreased in most patients, an effect lasting for a median of 24 h.

Systemic adenosine infusion reduces the area of tactile allodynia in neuropathic pain following peripheral nerve injury: a multi-centre, placebo-controlled study

Systemic adenosine has been shown in earlier case reports and a small placebo‐controlled study to reducepathological sensory dysfunction such as tactile allodynia in neuropathic pain. To evaluate this further, the effects of systemic adenosine infusion (50 μg/kg/min for 60 min) on tactile sensory dysfunction and pain was evaluated in 26 patients suffering peripheral neuropathic pain characterized by dynamic tactile allodynia. A randomized, cross‐over, double‐blind, placebo‐controlled technique was used in this multi‐centre study. Psychophysical methods were used to evaluate sensory dysfunction and spontaneous pain. The area of dynamic tactile allodynia was significantly reduced by adenosine compared with placebo (p=0.043), but spon‐taneous pain and tactile pain threshold were not significantly improved compared with the effects of placebo treatment. As a secondary outcome, a higher incidence of positive subjective effects on the clinical pain condi‐tion, in a few cases with long duration (several months), following adenosine treatment was found when theglobal effect of respective treatment was assessed (p=0.028). The results demonstrate involvement of adenosine receptor‐sensitive pain mechanisms in some aspects of the sensory dysfunction often found in neuropathic pain.

Procedure‐related pain among adult patients with hematologic malignancies

Background: Cancer patients undergo numerous invasive diagnostic procedures. However, there are only sparse data on the characteristics and determinants for procedure‐related pain among adult cancer patients.

Adult limb and breast amputees' experience and descriptions of phantom phenomena—A qualitative study

Abstract Background Phantom phenomena – pain or other sensations appearing to come from amputated body parts – are frequent consequences of amputation and can cause considerable suffering. Also, stump pain, located in the residual limb, is in the literature often related to the phantom phenomena. The condition is not specific to amputated limbs and has, to a lesser extent, been reported to be present after radical surgery in other body parts such as breast, rectum and teeth. Multi-causal theories are used when trying to understand these phenomena, which are recognized as the result of complex interaction among various parts of the central nervous system confirmed in studies using functional brain imaging techniques. Functional brain imaging has yielded important results, but without certainty being related to phantom pain as a subjective clinical experience. There is a wide range of treatment methods for the condition but no documented treatment of choice. Aims In this study a qualitative, explorative and prospective design was selected, in the aim to understand the patients’ personal experience of phantom phenomena. The research questions focused at how patients affected by phantom pain and or phantom sensations describe, understand, and live with these phenomena in their daily life. This study expanded ‘phantom phenomena’ to also encompass phantom breast phenomenon. Since the latter phenomenon is not as well investigated as the phantom limb, there is clinical concern that this is an underestimated problem for women who have had breasts removed. Methods The present study forms the first part of a larger, longitudinal study. Only results associated with data from the first interviews with patients, one month after an amputation, are presented here. At this occasion, 28 patients who had undergone limb amputation (20) or mastectomy (8) were interviewed. The focused, semi-structured interviews were recorded, transcribed, and then analyzed using discourse-narrative analysis. Results The interviewees had no conceptual problems in talking about the phenomena or distinguishing between various types of discomfort and discomfort episodes. Their experience originated from a vivid, functioning body that had lost one of its parts. Further, the interviewees reported the importance of rehabilitation and advances in prosthetic technology. Loss of mobility struck older amputees as loss of social functioning, which distressed them more than it did younger amputees. Phantom sensations, kinetic and kinesthetic perceptions, constituted a greater problem than phantom pain experienced from the amputated body parts. The descriptions by patients who had had mastectomies differed from those by patients who had lost limbs in that the phantom breast could be difficult to describe and position spatially. The clinical implication of this study is that when phantom phenomena are described as everyday experience, they become a psychosocial reality that supplements the definition of phantom phenomena in scientific literature and clinical documentation. Conclusions There is a need for clinical dialogues with patients, which besides, providing necessary information about the phenomena to the patients creates possibilities for health professionals to carefully listen to the patients’ own descriptions of which functional losses or life changes patients fear the most. There is a need for more qualitative studies in order to capture the extreme complexity of the pain–control system will be highlighted.

Phantom phenomena – Their perceived qualities and consequences from the patient's perspective

Abstract Background and aim The curious phenomenon phantom limbs early became the object of research, and its underlying mechanisms have been discussed over the years. The complex nature of phantom phenomena makes interpretation of the results ambiguous, regarding both prevalence and the accompanying suffering. There is a lack of knowledge about how amputees experience the meaning and consequences of phantom phenomena. The present aim, therefore, was to investigate how individuals, in an interview situation, described the qualities of possible perceived phantom phenomena, and how their experience affected their lives one month after the amputation/mastectomy. Methods Twenty-eight women and men who had undergone a limb amputation or mastectomy were interviewed. The focused, narrative-oriented interviews were transcribed verbatim and the scripts were analysed with content analysis. Results One month after the amputation the informants described and related their phantom pain and phantom sensations in sensory-discriminative, motivational-affective and cognitive-evaluative dimensions. The phantom sensations were experienced mainly as more agonizing than the phantom pain. Despite both the high intensity of and the high annoyance at the phantom pain and phantom sensations, a majority felt that the phantom phenomena were not a hindrance in their attempts to recapture ordinary life. But when the hindrance was evaluated as high, the annoyance was evaluated as the highest possible for both phenomena or for the phantom sensations alone, never for phantom pain alone. The interviewees’ reported attitudes of hindrance were also described and estimated in the light of their sociocultural circumstances. Thus, other preceding and/or co-existent pain conditions as well as factors such as pre-operative information, the respondents’ views on pain treatment, and their knowledge and understanding of phantom phenomena were mentioned and related to the pain-producing situation. Two-thirds of the interviewees had received post-surgical information and for some, the phenomena were well-known from earlier experience. A majority applied some version of the medical explanation model, irrespective of age or level of education. However neither information nor medical explanation, or both, sufficed for them to understand their own phantom phenomena. Thus, differences between the concepts explanation and understanding seemed significant for the annoyance related to the phantom phenomena. Regarding background data (i) the majority of the interviewees had had pre-amputation pain problems; (ii) the breast-cancer phantoms differed in several ways; (iii) there were some age and gender differences in the descriptions of hindrance. Conclusions and implications These findings highlight the importance of observing the individual approach to the phenomena as a process of evaluation and selection. In addition, experience and understanding of the phantoms also have sociocultural aspects. There follows the need for individualized communication and information from the clinician, and for incorporating a socioscientific and meaning-centred approach in future studies. The present insights could also be of value in other iatrogenic pain conditions.

The meaning and consequences of amputation and mastectomy from the perspective of pain and suffering

Abstract Background The concepts ‘pain’ and ‘suffering’ are frequently treated as synonymous. However, they are clearly distinct phenomena. Phantom phenomena including pain and sensory disturbances are still recognized as long-lasting problems after limb amputation and after mastectomy. The complex nature of phantom phenomena makes the interpretation of its results ambiguous, regarding the prevalence of pain, sensory disturbances and the accompanying suffering. There is clinical experience that suffering is a great burden for the individual but there is a lack of systematic studies of patients’ own evaluations of the suffering caused by their phantom phenomena. Objectives The overall aim of this study was to identify and describe patients’ suffering related to, and as a part, of their post-amputation situation. Methods The present study constitutes a part of a prospective, two-year follow up project investigating interviews of 28 men and women in different ages and who have undergone a limb amputation or mastectomy. The reason for amputation or mastectomy varied among the patients and included vascular diseases, cancer (sarcoma and breast-cancer) and trauma. Our ambition was to extract as much variations as possible in different, individualized aspects of the actual pain and suffering producing situation. The participants were, here, invited to open-ended, narrative-oriented interviews one month after the surgery. The interviews were transcribed verbatim and analyzed within qualitative methodology: thematic content analysis. Results Twenty-two of 28 interviewees experienced phantom pain and phantom sensations. The two surgical processes amputation and mastectomy meant for a majority of the interviewees a critical event with threatening consequences for everyday life such as loss of function and personal integrity. Nine interviewees felt even stigmatized as a result of their lost body part. Numerous inter-related factors following the amputation/mastectomy, which can inflict severe suffering on the amputee, were uncovered. The context in which the interviewees were informed about the decision to amputate proved to be one such critical and important factor. Conclusion To understand potential suffering in relation to phantom phenomena, it will never be enough merely to have knowledge of the underlying physiological or neurological mechanisms and/or the intensity of phantom pain and phantom sensations. Rather, it is necessary to find out how the loss of the body part and its everyday consequences are experienced by patients. Implications It is important to create time for real dialogue with the patients both during pre-operative preparation and post-operative rehabilitation in order to clarify and verbalize elements that constitute the patients individual suffering. Hopefully this strategy can alleviate future chronic pain problems, severe psycho-social distress and suffering. Such an approach ought to have impact also for perceived suffering after other types of surgery or different invasive treatments.

366 HOW WILL THE MODERN AMPUTEES DESCRIBE AND UNDERSTAND THE PHENOMENON OF A PHANTOM — A QUALITATIVE STUDY

Background and objectives: Pregabalin, an a2-delta ligand with analgesic, anxiolytic, and anticonvulsant activity, has been evaluated for treatment of neuropathic pain. It has been suggested that central neuronal sensitization may play an important role in postoperative pain. The aim of the study was to evaluate the effect of pregabalin versus placebo on postamputation pain and postoperative morphine consumption. Methods: Patients undergoing amputation for the upper or lower limbs were enrolled into this randomized double-blind study. 60 patients were divided into three groups to receive oral placebo, or pregabalin 300mg, or 600mg, 2 hours before surgery. Then followed by pregabalin 300mg, 600mg and placebo orally 8, 16, 24 h after the initial dose. Postoperatively patients received patient-controlled analgesia with morphine for 24 hours. Pain was assessed on a visual analogue scale and side effects were assessed four hourly for 24 hours postoperatively. Results: Mean pain scores were significantly reduced in patients receiving 300 and 600mg pregabalin compared with placebo at all time points. Additionally, pregabalin (300 and 600mg) reduced total morphine consumption from a median of 31 (interquartile range, 23–34) to 17 (12– 21)mg (P< 0.0001), and 38 (interquartile range 29–43) to 16 (10–19)mg (P< 0.0001) respectively. The most frequent side effect was excessive sedation with pregabalin 600mg group, yet this was not significant. Conclusion: Pregabalin provided a significant pain relief and significantly reduced morphine consumption postamputation. Future studies should evaluate the incidence of phantom limb pain after preemptive and repeated use of pregabalin.