Differential brain activity in subjects with painful trigeminal neuropathy and painful temporomandibular disorder.

Human brain imaging investigations have revealed that acute pain is associated with coactivation of numerous brain regions, including the thalamus, somatosensory, insular, and cingulate cortices. Surprisingly, a similar set of brain structures is not activated in all chronic pain conditions, particularly chronic neuropathic pain, which is associated with almost exclusively decreased thalamic activity. These inconsistencies may reflect technical issues or fundamental differences in the processing of acute compared with chronic pain. The appreciation of any differences is important because better treatment development will depend on understanding the underlying mechanisms of different forms of pain. In this investigation, we used quantitative arterial spin labeling to compare and contrast regional cerebral blood flow (CBF) patterns in individuals with chronic neuropathic orofacial pain (painful trigeminal neuropathy) and chronic nonneuropathic orofacial pain (painful temporomandibular disorder). Neuropathic pain was associated with CBF decreases in a number of regions, including the thalamus and primary somatosensory and cerebellar cortices. In contrast, chronic nonneuropathic pain was associated with significant CBF increases in regions commonly associated with higher-order cognitive and emotional functions, such as the anterior cingulate and dorsolateral prefrontal cortices and the precuneus. Furthermore, in subjects with nonneuropathic pain, blood flow increased in motor-related regions as well as within the spinal trigeminal nucleus.

Different pain, different brain: thalamic anatomy in neuropathic and non-neuropathic chronic pain syndromes.

Trigeminal neuropathic pain (TNP) and temporomandibular disorders (TMD) are thought to have fundamentally different etiologies. It has been proposed that TNP arises through damage to, or pressure on, somatosensory afferents in the trigeminal nerve, whereas TMD results primarily from peripheral nociceptor activation. Because some reports suggest that neuropathic pain is associated with changes in brain anatomy, it is possible that TNP is maintained by changes in higher brain structures, whereas TMD is not. The aim of this investigation is to determine whether changes in regional brain anatomy and biochemistry occur in both conditions. Twenty-one TNP subjects, 20 TMD subjects, and 36 healthy controls were recruited. Voxel-based morphometry of T1-weighted anatomical images revealed no significant regional gray matter volume change in TMD patients. In contrast, gray matter volume of TNP patients was reduced in the primary somatosensory cortex, anterior insula, putamen, nucleus accumbens, and the thalamus, whereas gray matter volume was increased in the posterior insula. The thalamic volume decrease was only seen in the TNP patients classified as having trigeminal neuropathy but not those with trigeminal neuralgia. Furthermore, in trigeminal neuropathy patients, magnetic resonance spectroscopy revealed a significant reduction in the N-acetylaspartate/creatine ratio, a biochemical marker of neural viability, in the region of thalamic volume loss. The data suggest that the pathogenesis underlying neuropathic and non-neuropathic pain conditions are fundamentally different and that neuropathic pain conditions that result from peripheral injuries may be generated and/or maintained by structural changes in regions such as the thalamus.

Changes in human primary motor cortex activity during acute cutaneous and muscle orofacial pain.

AIMS: To use functional magnetic resonance imaging (fMRI) to determine whether orofacial cutaneous or muscle pain is associated with changes in primary motor cortex (M1) activity that outlast the duration of perceived pain, and whether these M1 changes are different during cutaneous pain compared with muscle pain. METHODS: fMRI was used in healthy subjects experiencing orofacial muscle (n = 17) or cutaneous (n = 15) pain induced by bolus injections of hypertonic saline (4.5%) into the belly of the masseter muscle (0.5 ml) or subcutaneously (0.2 ml) into the overlying skin, respectively. To determine the effects of the injection volume, isotonic saline (n = 4) was injected into the masseter muscle. RESULTS: Similar pain scores were observed following subcutaneous (mean [± SEM]; 4.73 ± 0.51) or intramuscular injections (4.35 ± 0.56). Orofacial muscle but not cutaneous pain was associated with a transient increase in signal intensity in the contralateral M1. Cutaneous and muscle orofacial pains were associated with similar signal intensity decreases within the contralateral M1 that continued to decrease for the entire scanning period. Isotonic saline did not evoke pain or changes in M1 signal intensity. CONCLUSION: The transient contralateral M1 signal intensity increase during orofacial muscle pain may underlie escape-like motor patterns. However, once the initial threat has subsided, longer-term reductions in M1 activity and/or excitability may occur to aid in minimizing movement of the affected part, an effect consistent with the general proposals of the Pain Adaptation Model.

Differential activation of the human trigeminal nuclear complex by noxious and non-noxious orofacial stimulation.

There is good evidence from animal studies for segregation in the processing of non-nociceptive and nociceptive information within the trigeminal brainstem sensory nuclear complex. However, it remains unknown whether a similar segregation occurs in humans, and a recent tract tracing study suggests that this segregation may not exist. We used functional magnetic resonance imaging (fMRI) to define and compare activity patterns of the trigeminal brainstem nuclear complex during non-noxious and noxious cutaneous and non-noxious and noxious muscle orofacial stimulation in humans. We found that during cutaneous pain, signal intensity increased within the entire rostrocaudal extent of the spinal trigeminal nucleus (SpV), encompassing the ipsilateral oralis (SpVo), interpolaris (SpVi) and caudalis (SpVc) subdivisions. In contrast, muscle pain did not activate SpVi, but instead activated a discrete region of the ipsilateral SpVo and SpVc. Further, muscle noxious stimulation activated a region of the ipsilateral lateral pons in the region of the trigeminal principal sensory nucleus (Vp). Innocuous orofacial stimulation (lip brushing) also evoked a significant increase in signal intensity in the ipsilateral Vp; however, non-noxious muscle stimulation showed no increase in signal in this area. The data reveal that orofacial cutaneous and muscle nociceptive information and innocuous cutaneous stimulation are differentially represented within the trigeminal nuclear complex. It is well established that cutaneous and muscle noxious stimuli evoke different perceptual, behavioural and cardiovascular changes. We speculate that the differential activation evoked by cutaneous and muscle noxious stimuli within the trigeminal sensory complex may contribute to the neural basis for these differences.