Interleukin-6 induces spatially dependent whole-body hypersensitivity in rats: implications for extracephalic hypersensitivity in migraine
Abstract Background Migraine is a complex neurological disorder that is characterized by throbbing head pain, increased sensitivity to light, sound, and touch, as well as nausea and fatigue. It is one of the most common and most disabling disorders globally but mechanisms causing migraine are poorly...
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| Format: | Article |
| Language: | English |
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BMC
2021-07-01
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| Series: | The Journal of Headache and Pain |
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| Online Access: | https://doi.org/10.1186/s10194-021-01286-8 |
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| author | Amanda Avona Theodore J Price Gregory Dussor |
| author_facet | Amanda Avona Theodore J Price Gregory Dussor |
| author_sort | Amanda Avona |
| collection | DOAJ |
| description | Abstract Background Migraine is a complex neurological disorder that is characterized by throbbing head pain, increased sensitivity to light, sound, and touch, as well as nausea and fatigue. It is one of the most common and most disabling disorders globally but mechanisms causing migraine are poorly understood. While head pain is a typical feature of attacks, they also often present with cutaneous hypersensitivity in the rest of the body. In contrast, primary pain conditions in the lower parts of the body are less commonly associated with cephalic hypersensitivity. Previous studies indicate that application of stimuli to the meninges of rodents causes cutaneous facial as well as hindpaw hypersensitivity. In the present study, we asked whether widespread hypersensitivity is a unique feature of dural stimulation or whether body-wide responses occur similarly when the same stimulus is given in other locations. Methods Rats were given the same dose of IL-6 either via dural, intraplantar, subcutaneous, intramuscular, intracisternal, or intrathecal injection. Cutaneous facial and hindpaw allodynia was assessed using Von Frey following injection into each location. Results Hindpaw allodynia was observed following dural and intraplantar injection of IL-6 in both males and females. Hindpaw allodynia was only observed in females following intracisternal and intrathecal IL-6 injections. In contrast, facial allodynia was only observed in either sex following dural and intracisternal injections, which would activate meningeal afferents and the trigeminal nucleus caudalis (TNC), respectively. Conclusions Here we show that while stimulation of upper body regions with IL-6 including the meninges and brainstem can cause widespread hypersensitivity spreading to the paws, similar stimulation of the lower body does not cause the spread of hypersensitivity into the head. These data are consistent with the observations that whole body hypersensitivity is specific to conditions such as migraine where pain is present in the head and they may provide insight into co-morbid pain states associated with migraine. |
| first_indexed | 2024-12-17T02:16:59Z |
| format | Article |
| id | doaj.art-f71f0ab8c5dc40f58c2ed41fc6a87211 |
| institution | Directory Open Access Journal |
| issn | 1129-2369 1129-2377 |
| language | English |
| last_indexed | 2024-12-17T02:16:59Z |
| publishDate | 2021-07-01 |
| publisher | BMC |
| record_format | Article |
| series | The Journal of Headache and Pain |
| spelling | doaj.art-f71f0ab8c5dc40f58c2ed41fc6a872112022-12-21T22:07:23ZengBMCThe Journal of Headache and Pain1129-23691129-23772021-07-0122111210.1186/s10194-021-01286-8Interleukin-6 induces spatially dependent whole-body hypersensitivity in rats: implications for extracephalic hypersensitivity in migraineAmanda Avona0Theodore J Price1Gregory Dussor2School of Behavioral and Brain Sciences, Center for Advanced Pain Studies, University of Texas at DallasSchool of Behavioral and Brain Sciences, Center for Advanced Pain Studies, University of Texas at DallasSchool of Behavioral and Brain Sciences, Center for Advanced Pain Studies, University of Texas at DallasAbstract Background Migraine is a complex neurological disorder that is characterized by throbbing head pain, increased sensitivity to light, sound, and touch, as well as nausea and fatigue. It is one of the most common and most disabling disorders globally but mechanisms causing migraine are poorly understood. While head pain is a typical feature of attacks, they also often present with cutaneous hypersensitivity in the rest of the body. In contrast, primary pain conditions in the lower parts of the body are less commonly associated with cephalic hypersensitivity. Previous studies indicate that application of stimuli to the meninges of rodents causes cutaneous facial as well as hindpaw hypersensitivity. In the present study, we asked whether widespread hypersensitivity is a unique feature of dural stimulation or whether body-wide responses occur similarly when the same stimulus is given in other locations. Methods Rats were given the same dose of IL-6 either via dural, intraplantar, subcutaneous, intramuscular, intracisternal, or intrathecal injection. Cutaneous facial and hindpaw allodynia was assessed using Von Frey following injection into each location. Results Hindpaw allodynia was observed following dural and intraplantar injection of IL-6 in both males and females. Hindpaw allodynia was only observed in females following intracisternal and intrathecal IL-6 injections. In contrast, facial allodynia was only observed in either sex following dural and intracisternal injections, which would activate meningeal afferents and the trigeminal nucleus caudalis (TNC), respectively. Conclusions Here we show that while stimulation of upper body regions with IL-6 including the meninges and brainstem can cause widespread hypersensitivity spreading to the paws, similar stimulation of the lower body does not cause the spread of hypersensitivity into the head. These data are consistent with the observations that whole body hypersensitivity is specific to conditions such as migraine where pain is present in the head and they may provide insight into co-morbid pain states associated with migraine.https://doi.org/10.1186/s10194-021-01286-8MigraineCephalic hypersensitivityInterleukin-6HeadacheReferred hypersensitivityAllodynia |
| spellingShingle | Amanda Avona Theodore J Price Gregory Dussor Interleukin-6 induces spatially dependent whole-body hypersensitivity in rats: implications for extracephalic hypersensitivity in migraine The Journal of Headache and Pain Migraine Cephalic hypersensitivity Interleukin-6 Headache Referred hypersensitivity Allodynia |
| title | Interleukin-6 induces spatially dependent whole-body hypersensitivity in rats: implications for extracephalic hypersensitivity in migraine |
| title_full | Interleukin-6 induces spatially dependent whole-body hypersensitivity in rats: implications for extracephalic hypersensitivity in migraine |
| title_fullStr | Interleukin-6 induces spatially dependent whole-body hypersensitivity in rats: implications for extracephalic hypersensitivity in migraine |
| title_full_unstemmed | Interleukin-6 induces spatially dependent whole-body hypersensitivity in rats: implications for extracephalic hypersensitivity in migraine |
| title_short | Interleukin-6 induces spatially dependent whole-body hypersensitivity in rats: implications for extracephalic hypersensitivity in migraine |
| title_sort | interleukin 6 induces spatially dependent whole body hypersensitivity in rats implications for extracephalic hypersensitivity in migraine |
| topic | Migraine Cephalic hypersensitivity Interleukin-6 Headache Referred hypersensitivity Allodynia |
| url | https://doi.org/10.1186/s10194-021-01286-8 |
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