Brain processing of capsaicin-induced secondary hyperalgesia

Baron, Ralf; Baron, Yvonne; Disbrow, Elizabeth A.; Roberts, Timothy P. L.

doi:10.1212/wnl.53.3.548

Cited by 172 publications

(99 citation statements)

References 43 publications

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“…Furthermore, SI activity was significantly correlated with the intensity of pain that was experienced on a trial-by-trial basis in the normal state as well as during CS. These findings suggest that the increased cortical activity found in SI and ACC in previous neuroimaging studies of secondary mechanical hyperalgesia (Iadarola et al, 1998;Baron et al, 1999;Zambreanu et al, 2005;Mainero et al, 2007) mainly reflects the increased intensity of pain experienced during CS.…”

Section: Increased Pain Intensity As the Perceptual Consequence Of Cesupporting

confidence: 51%

“…A specific role for the brainstem in the maintenance of central sensitization Several imaging laboratories, including ours, have mapped widespread increases in brain activity to an identical force of punctate stimulation in the hyperalgesic state compared with the normal state (Baron et al, 1999;Zambreanu et al, 2005). However, amplification of input from peripheral mechanosensitive afferents occurs at the level of the spinal dorsal horn (Sun et al, 2004) before further transmission to supraspinal areas.…”

Section: Discussionmentioning

confidence: 97%

“…Nearly a decade of neuroimaging research has revealed that supraspinal activity is increased during mechanical hyperalgesia that is experimentally induced by capsaicin in healthy volunteers (Iadarola et al, 1998;Baron et al, 1999;Zambreanu et al, 2005;Mainero et al, 2007). Increased activity is found in the brainstem, the thalami, cerebellum, primary and secondary somatosensory cortices, insula and cingulate cortex.…”

Section: Introductionmentioning

confidence: 99%

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Identifying Brain Activity Specifically Related to the Maintenance and Perceptual Consequence of Central Sensitization in Humans

Lee¹,

Zambreanu²,

Menon³

et al. 2008

J. Neurosci.

142

106

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Central sensitization (CS) refers to an increase in the excitability of spinal dorsal horn neurons that results from, and far outlasts the initiating nociceptive input. Here, functional magnetic resonance imaging was used to examine whether supraspinal activity might contribute to the maintenance of CS in humans. A crossover parametric design was used to distinguish and control for brain activity that is related to the consequence of increased pain experienced during CS. When the intensity of pain during CS and normal states were matched, only activity within the brainstem, including the mesencephalic pontine reticular formation, and the anterior thalami remained increased during CS. Further analyses revealed that activity in the isolated brainstem area correlated positively with the force of noxious stimulation only during CS, whereas activity in the isolated thalamic area was not modulated parametrically in either CS or normal states. Additionally, the mean activity in the isolated brainstem area was increased only during CS, whereas the mean activity in the isolated thalamic area was increased in both states, albeit less so in the normal state. Together, these findings suggest a specific role of the brainstem for the maintenance of CS in humans. Regarding brain areas related to the consequence of increased pain perception during CS, we found that only cortical activity, mainly in the primary somatosensory area, was significantly correlated with intensity of pain that was attributable to both the force of noxious stimulation used and state in which noxious stimulation was applied.

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Section: Increased Pain Intensity As the Perceptual Consequence Of Cesupporting

confidence: 51%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Identifying Brain Activity Specifically Related to the Maintenance and Perceptual Consequence of Central Sensitization in Humans

Lee¹,

Zambreanu²,

Menon³

et al. 2008

J. Neurosci.

142

106

View full text Add to dashboard Cite

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“…Activations in S2 are commonly found during painful stimulation (42), but are not specific to the evoked pain. Activity in S2 has been described after nonpainful tactile (43), electrical (44), and vibratory stimulation (45), and thus S2 is considered to be a somatosensory integrative area.…”

Section: Discussionmentioning

confidence: 99%

Evidence of augmented central pain processing in idiopathic chronic low back pain

Giesecke¹,

Gracely²,

Grant³

et al. 2004

Arthritis & Rheumatism

716

456

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Objective. For many individuals with chronic low back pain (CLBP), there is no identifiable cause. In other idiopathic chronic pain conditions, sensory testing and functional magnetic resonance imaging (fMRI) have identified the occurrence of generalized increased pain sensitivity, hyperalgesia, and altered brain processing, suggesting central augmentation of pain processing in such conditions. We compared the results of both of these methods as applied to patients with idiopathic CLBP (n ‫؍‬ 11), patients with widespread pain (fibromyalgia; n ‫؍‬ 16), and healthy control subjects (n ‫؍‬ 11).Methods. Patients with CLBP had low back pain persisting for at least 12 months that was unexplained by MRI/radiographic changes. Experimental pain testing was performed at a neutral site (thumbnail) to assess the pressure-pain threshold in all subjects. For fMRI studies, stimuli of equal pressure (2 kg) and of equal subjective pain intensity (slightly intense pain) were applied to this same site.Results. Despite low numbers of tender points in the CLBP group, experimental pain testing revealed hyperalgesia in this group as well as in the fibromyalgia group; the pressure required to produce slightly intense pain was significantly higher in the controls (5.6 kg) than in the patients with CLBP (3.9 kg) (P ‫؍‬ 0.03) or the patients with fibromyalgia (3.5 kg) (P ‫؍‬ 0.006).When equal amounts of pressure were applied to the 3 groups, fMRI detected 5 common regions of neuronal activation in pain-related cortical areas in the CLBP and fibromyalgia groups (in the contralateral primary and secondary [S2] somatosensory cortices, inferior parietal lobule, cerebellum, and ipsilateral S2). This same stimulus resulted in only a single activation in controls (in the contralateral S2 somatosensory cortex). When subjects in the 3 groups received stimuli that evoked subjectively equal pain, fMRI revealed common neuronal activations in all 3 groups.Conclusion. At equal levels of pressure, patients with CLBP or fibromyalgia experienced significantly more pain and showed more extensive, common patterns of neuronal activation in pain-related cortical areas. When stimuli that elicited equally painful responses were applied (requiring significantly lower pressure in both patient groups as compared with the control group), neuronal activations were similar among the 3 groups. These findings are consistent with the occurrence of augmented central pain processing in patients with idiopathic CLBP.Chronic low back pain (CLBP) is one of the most common and expensive musculoskeletal disorders in developed countries (1,2). Back pain in general affects 70-85% of all people at some time in their lives, but 90% of affected individuals recover, typically within 12 weeks (3). Recovery after 12 weeks is slow and uncertain, and this subset of patients with CLBP accounts for major expenses in the health care and disability systems (2,4).Despite the magnitude of the problem, little is known about the precise cause of CLBP. There is often a mismatch between objectiv...

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“…In addition, descending facilitatory influences have been suggested to underlie chronic pain states (36,37). Some studies have recently investigated the brain responses to somatosensory stimuli delivered to an area of secondary hyperalgesia during central sensitization, in normal subjects and in patients (24,33,(38)(39)(40). The results of these studies are somewhat contrasting, mainly because of the different kind of somatosensory stimulation delivered (innocuous brushing, punctate stimulation of different intensities) and the investigation technique chosen (fMRI, PET, MEG).…”

Section: Discussionmentioning

confidence: 99%

Pharmacological modulation of pain-related brain activity during normal and central sensitization states in humans

Iannetti

Zambreanu

Wise

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

250

203

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Abnormal processing of somatosensory inputs in the central nervous system (central sensitization) is the mechanism accounting for the enhanced pain sensitivity in the skin surrounding tissue injury (secondary hyperalgesia). Secondary hyperalgesia shares clinical characteristics with neurogenic hyperalgesia in patients with neuropathic pain. Abnormal brain responses to somatosensory stimuli have been found in patients with hyperalgesia as well as in normal subjects during experimental central sensitization. The aim of this study was to assess the effects of gabapentin, a drug effective in neuropathic pain patients, on brain processing of nociceptive information in normal and central sensitization states. Using functional magnetic resonance imaging (fMRI) in normal volunteers, we studied the gabapentin-induced modulation of brain activity in response to nociceptive mechanical stimulation of normal skin and capsaicin-induced secondary hyperalgesia. The dose of gabapentin was 1,800 mg per os, in a single administration. We found that (i) gabapentin reduced the activations in the bilateral operculoinsular cortex, independently of the presence of central sensitization; (ii) gabapentin reduced the activation in the brainstem, only during central sensitization; (iii) gabapentin suppressed stimulus-induced deactivations, only during central sensitization; this effect was more robust than the effect on brain activation. The observed drug-induced effects were not due to changes in the baseline fMRI signal. These findings indicate that gabapentin has a measurable antinociceptive effect and a stronger antihyperalgesic effect most evident in the brain areas undergoing deactivation, thus supporting the concept that gabapentin is more effective in modulating nociceptive transmission when central sensitization is present.deactivation ͉ fMRI ͉ hyperalgesia ͉ nociceptive system A fter skin injury, an increased sensitivity to mechanical stimuli occurs in a large, uninjured area surrounding the injury site (1, 2). This phenomenon is termed secondary hyperalgesia and is the consequence of neuroplastic changes leading to a state of sensitization of the central nervous system (central sensitization) (3). Secondary hyperalgesia can be experimentally induced by treating the skin with high doses of the vanilloid capsaicin (by intradermal injection or topical application).Two forms of mechanical hyperalgesia occur in the area of secondary hyperalgesia: hyperalgesia to gentle skin stroking (stroking hyperalgesia or allodynia) and hyperalgesia to punctate stimuli (punctate hyperalgesia). Although both stroking and punctate hyperalgesia are due to central sensitization, they have different psychophysical characteristics (punctate hyperalgesia is easier to establish, it encompasses a larger area and it is longer-lasting than stroking hyperalgesia). They are mediated by different primary afferents (3): stroking hyperalgesia is signaled by low-threshold mechanoreceptors (4), whereas punctate hyperalgesia is signaled by capsaicin-insensitive A-fi...

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Brain processing of capsaicin-induced secondary hyperalgesia

Cited by 172 publications

References 43 publications

Identifying Brain Activity Specifically Related to the Maintenance and Perceptual Consequence of Central Sensitization in Humans

Identifying Brain Activity Specifically Related to the Maintenance and Perceptual Consequence of Central Sensitization in Humans

Evidence of augmented central pain processing in idiopathic chronic low back pain

Pharmacological modulation of pain-related brain activity during normal and central sensitization states in humans

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