Functional brain imaging of acute postoperative pain
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Satu K. Jääskeläinen
Since the early 1990s when modern functional imaging techniques, such as positron emission tomography (PET) suitable for detailed studies on the living human brain and its reactions to external stimuli, were introduced to the study of pain, huge steps have been taken towards understanding the important role of supraspinal systems and mechanisms involved in the perception, cognitive, attentional and emotional processing, as well as top-down modulation of pain in health and disease [1,2]. PET and, slightly later, functional magnetic resonance imaging (fMRI) have offered non-invasive means to elucidate the relative increases or decreases in regional cerebral blood flow (rCBF; PET and fMRI) or metabolic activity (PET) of different brain areas after pain-inducing or analgesic interventions in comparison to baseline. Depending on the study design, these techniques have allowed evaluation of the effects of emotional and cognitive tasks and states on the activation/deactivation patterns associated to either pain or analgesia.
The interpretation of PET and fMRI findings is based on the assumption that a relative increase in rCBF (or metabolic rate) is coupled to neuronal activation and a decrease in blood flow to decreased neuronal firing when compared to baseline. The alterations do not specify, however, whether the neurons activated or inhibited are excitatory or inhibitory in nature. Thus, no firm conclusions can be drawn about the direct local functional consequences of the observed changes in regional blood flow and neuronal firing although the net effects on nociception and pain can be psychophysically measured. Nevertheless, neuroimaging studies have elucidated the complex network of structures in the brain changing their action during pain, the interconnected cortical areas and subcortical nuclei each playing a distinct role in parallel processing of various aspects of nociception, pain, and suffering.
The group of Andersson, Gordh and Torebjörk [3] has participated in this important earlier work, e.g. by showing somatotopic organisation along the central sulcus for localisation of painful stimuli. This previous study, as most of the neuroimaging studies on pain and its modulation so far, was done in healthy subjects whose pain was experimental and adaptive mechanisms were intact. Even now, less is known about maladaptive system functions in pathological clinical pain conditions [4].
The article by Gordh et al., “Brain activation due to postoperative pain from the right hand measured with regional cerebral blood flow using positron emission tomography” published in this issue of SJP [5], tackles the problem by analysing similarities and differences between acute post-surgical pain and its relief in chronic, non-neuropathic pain patients, in comparison to an earlier experimental pain study [3] utilising the same PET method. The current patients were operated on for osteoarthritis of the carpometacarpal joint, and their rCBF was analysed during acute postoperative pain and immediately after complete pain relief with local anaesthetic blockade. The aim of the current paper has importance since surgical pain seems to offer an appealing and relevant human pain “model” that is increasingly used in clinical studies for understanding chronic and neuropathic human pain [6]. There is one earlier study on post-procedural, acute inflammatory pain related to tooth extraction [8], and another patient case report on postoperative pain [7], but surgical pain has not previously been systematically studied with modern brain imaging techniques.
The ambitious study design of the current paper by Gordh et al. [5] is fascinating and new and, although the number of patients is small, the results are significant showing alterations in brain activity of various brain regions during acute post-surgical pain compared to pain free condition. The results are discussed highlighting the partially shared, partially distinct patterns of activation and deactivation when compared to the previous study with similar PET design on experimental human pain [3], and to other brain imaging studies on experimental and clinical pain conditions and anxiety.
Functional brain imaging has shown that clinical pain differs in many aspects from experimental pain as regards the brain structures relatively activated or inactivated; e.g. rCBF is decreased in contralateral thalamus and anterior cingulate cortex (ACC), but often increased in prefrontal areas in chronic pain patients subjected to painful stimuli, whereas opposite alterations are more frequently observed in experimental pain showing nearly constantly an increase in thalamic, insular, and ACC flow, but less frequently increases in prefrontal areas after noxious stimuli [1].
In the present study, similar to nociceptive experimental conditions (but unlike some chronic pain conditions such as neuropathic pain), primary and secondary somatosensory and motor cortices contralateral to the painful area participating in the localisation and intensity coding of painful input were clearly activated during acute postoperative pain. Thus, function of these brain structures involved in the sensory-discriminative process was not altered by chronic osteoarthritis and neither did post-surgical noxious input differ in this respect from experimental pain stimuli.
However, in these patients, insular cortex was not activated nor deactivated during pain, although it has most consistently been reported to be active in pain [2]. Due to preoperative chronic osteoarthritis, adaptive behaviour of the pain network in these patients may have been altered already before the operation, which could explain some of the observed brain activation/deactivation patterns within the frontal regions. For example, relative decrease in blood flow of the anterior cingulate and prefrontal cortices found in this study during pain compared to pain free condition could be due to relative inactivity of excitatory neurons within these areas thought to participate in attentional, affective, motivational, and cognitive aspects of pain processing [4]. Alternatively, this rCBF change could also reflect relative inactivity of inhibitory neurons within these pain controlling areas during pain, with a consequent net excitation at the subsequent levels of the pain network, resulting in pronounced pain experience due to deficits in top-down control mechanisms. Furthermore, the authors discuss the relative decreases in the rCBF within the prefrontal areas of their patients during pain as an interesting analogy to what has been reported in PET studies on provoked anxiety.
In this small group of female patients, it was not possible to analyse in more detail the possible variation in the patterns of rCBF changes between subjects. Considerable variations in individual brain responses to experimental or clinical pain and analgesic treatment are starting to get more attention in brain imaging studies on pain, and large groups of patients including both sexes are needed in order to investigate the sources of this variability. Analysis of between-subjects factors with follow-up brain imaging would allow assessment of brain level patterns possibly specific for chronification of postoperative pain.
The most fascinating aspect of PET method is the possibility for in depth in vivo analysis of the function and dysfunction of specific neurotransmitter systems and their interconnections in clinical pain conditions. As a method for study of mere brain activation/deactivation patterns, rather expensive PET method exposing patients to radiation may not be the most adequate tool. fMRI offers similar data with better spatial and temporal resolution without the burden of radiation, allowing unlimited number of repeated examinations, which would be useful in long-term follow-up of patients in larger studies of the present type. The pilot study by Gordh et al. [5] shows that acute surgical patients can be studied with neuroimaging techniques opening the venue for application of this clinically valid human model to prospective in vivo evaluation of the brain mechanisms leading to persistence of post-traumatic pain.
DOI of refers to article: 10.1016/j.sjpain.2010.05.036.
References
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[5] Gordh T, Vinnars B, Fischer H, Blomberg H, Modig J, Fredrikson M, Hartvig P. Brain activation due to postoperative pain from the right hand measured with regional cerebral blood flow using positron emission tomography. Scand J Pain 2010;1:115–9.Search in Google Scholar
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© 2010 Scandinavian Association for the Study of Pain
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Articles in the same Issue
- Editorial comment
- Functional brain imaging of acute postoperative pain
- Clinical pain research
- Brain activation due to postoperative pain from the right hand measured with regional cerebral blood flow using positron emission tomography
- Editorial comment
- Long-term low-dose transdermal buprenorphine therapy for chronic noncancer pain
- Original experimental
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- Editorial comment
- Repeated nociceptive stimulation for detecting drug effects
- Original experimental
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- Observational studies
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- Observational studies
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- Abstracts
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- Abstracts
- What’s wrong with animal models of pain?
- Abstracts
- Immunotherapy for neuroblastoma elicits a complement dependent whole body allodynia
- Abstracts
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- Abstracts
- Translating basic research to pharmacological treatment of neuropathic pain
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- Free Poster Presentations: Forearm heat pain does not inhibit electrically induced tibialis anterior muscle pain
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