We investigated the neurobiological substrates associated with chronic low back pain due to lumbar disc herniation using [99mTc]Tc-ECD brain SPECT in 14 patients with a mean age of 40 years compared with ten healthy controls. The results revealed rCBF increase in the right frontal, occipital and posterior cingulate cortex, and rCBF decrease in the superior parietal lobe and middle cingulate cortex in patients with CLBP in patients with CLBP. Numeric rating scale of pain was inversely and moderately correlated with the intensity of rCBF increase in the right frontal lobe, and no correlation was observed between rCBF changes and douleur neuropathique en 4 questions.
An American epidemiological study showed a higher prevalence of CLBP among adults in the 5th and 6th decades of life (Shmagel, Foley, and Ibrahim 2016). Other studies have shown a higher incidence of CLBP in the third decade of life, with prevalence increasing until the age of 65 when it falls again (Loney and Stratford 1999), (Waxman, Tennant, and Helliwell 2000), (Hoy et al. 2010). A population study involving more than 10,000 volunteers in Portugal showed that CLBP prevalence increases significantly with age. Whereas the age group 36–45 years old had an estimated prevalence of CLBP in 7.2%, this proportion increased to 29.7% in the group above 86 years old (Gouveia et al. 2016a).
This study found a mean of 5.7 points on the NRS scale, close to the 6.0 points of a similar study that showed higher scores in women (6.2 ± 2.53) than men (5.7 ± 2.29) (Gouveia et al. 2016b). Nakamura et al. (2014) evaluated patients with acute and chronic low back pain and found a mean NRS of 6.3 (Nakamura et al. 2014b). Interestingly, Hiyama et al. (2015) found that CLBP patients with neuropathic disease reported NRS of 7.4 (± 1.9) points, while patients with nociceptive disease reported NRS of 5.1 (± 2.0). They also found that cases with either nociceptive or neuropathic CLBP present greater severity of pain than acute and subacute cases (Hiyama et al. 2015).
The pain was also assessed by the Douleur Neuropathique en 4 Questions (DN4), which was validated for Portuguese by Santos et al. (2010). DN4 seems, in this study, to help identify a neuropathic pain component in a consecutive population of patients with chronic pain in a moderate way (median DN4 scores 5.0; IQR 2 to 6.2) (Timmerman et al. 2017a).
The validity of DN4-signs is equal to the DN4 outcome, and, more importantly, both are more valid than the DN4-symptoms alone. It seems that the patients’ symptoms and signs don’t reliably reflect the underlying mechanisms, indicating that there is a need for a more objective way to assess patients’ pain to facilitate improvement in the treatment of patients with CLBP. The physicians’ assessment cannot be replaced by a screening tool as the DN4, but it gives the physician a slight hint towards the (non-)existence of the neuropathic pain component (Timmerman et al. 2017b).
Considering the brain SPECT findings of patients with CLBP, there was a significant rCBF increase in the right hemisphere, involving the right occipital and posterior cingulate areas, right middle and inferior frontal gyri, besides the right opercular frontal area. Nakamura et al. (2014) found increased blood flow in the bilateral posterior lobe of the cerebellum in patients with CLBP, whose pain had continued for more than six months despite conventional medical treatment and with indigent structural abnormalities (Nakamura et al. 2014c). Recent fMRI studies with CLBP patients during rest have demonstrated increased activation in the medial prefrontal cortex, cingulate cortex, amygdala, insula, and sensory-motor integration regions, together with a disrupted default mode network (DMN) (Kregel et al. 2015). In another fMRI study, older disabled CLBP patients presented activation of the right mesial prefrontal cortex at rest, whereas the non-disabled demonstrated activation of the left lateral prefrontal cortex (Buckalew et al. 2010).
The posterior cingulate cortex is a region traditionally linked to visuospatial orientation (Vogt, Derbyshire, and Jones 1996), episodic memory and pleasant stimuli (Maddock 1999), major depression (Ho et al. 1996), and anxiety (Reiman n.d.). Hsieh et al. (1995) found an rCBF increase in the posterior cingulate cortex of patients with chronic neuropathic pain and the right anterior cingulate cortex, suggesting its participation in the affective-motivational aspect of pain. They described a possible tendency to lateralization to the right hemisphere of the affective processes involved in chronic neuropathic pain (Hsieh et al. 1995). Other studies have also demonstrated the right lateralization of affective processes involved in chronic neuropathic pain (Hari et al. 1997) (Neri and Agazzani 1984).
Functional neuroimaging techniques, like SPECT and arterial spin labeling (ASL), assess regional cerebral flow and can be used to obtain task-free information according to the ongoing brain activity that may reflect natural pain characteristics of chronic pain (Davis and Moayedi 2013a). Previous studies described activated brain areas in response to pain. These constitute the “pain matrix”: the primary and secondary somatosensory cortices (S1, S2), the insular cortex (IC), the anterior cingulate cortex (ACC), the thalamus, and the prefrontal cortex (PFC) (Davis and Moayedi 2013b).
The present study showed decreased rCBF in a cluster including both parietal lobes and the right cingulate gyrus. Previous studies have shown that both the posterior parietal region and dorsolateral prefrontal cortex are involved in the cognitive-discriminative aspect of pain (Peyron et al. 1999), with an asymmetric predominance of involvement in the right hemisphere (Derbyshire et al. 1994) (Derbyshire and Jones 1998). CBLP patients exhibited reduced rCBF on the bilateral prefrontal cortex and increased rCBF in posterior lobes of the cerebellum (Nakamura et al. 2014d). Furthermore, reduction in resting DMN connectivity to the medial prefrontal cortex, including pregenual anterior cingulate cortex (pgACC), was described after physical maneuvers that exacerbate clinical back pain in CLBP patients. The pgACC is a region involved in pain inhibition due to its descending projections to periaqueductal gray matter (Loggia et al. 2013).
Neuroimaging studies involving the evaluation of neuropathic pain show heterogeneous patterns of brain activation. These probably reflect patients’ heterogeneity in etiology of pain, lesion topography, symptoms, and stimulation procedures for activation neuroimaging studies (Moisset and Bouhassira 2007). Also, the interpretation of results should consider the history of pain, anatomical distribution, genetic constitution, and personality, which may alter the cerebral circuits involved in chronic pain processes (Kupers and Kehlet 2006).
Strengths And Limitations
The present study’s findings contribute to the investigation of the neurobiological substrates of chronic lumbar back pain. Knowing the brain systems involved in CLBP and the functional activation and deactivation of these structures during the pain may represent the background for future pharmacokinetics and pharmacodynamic modeling studies. A limitation is the small sample of patients and healthy controls undergoing the study. However, the quantitative SPM technique offered sophisticated analysis tools that dispensed large samples, avoiding unnecessary exposure of patients to radiation. The group of participants with CLBP had a slightly older mean age than the control group.