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Persistent changes in spinal cord gene expression after recovery from inflammatory hyperalgesia: a preliminary study on pain memory.

Yukhananov R, Kissin I - BMC Neurosci (2008)

Bottom Line: Out of 17,000 annotated genes, 356 were found to be differentially expressed compared with the control group at 28d, and 329 at 24h after carrageenan injection (both groups at p < 0.01).Using gene ontology (GO) classification, we have identified 3 functional classes deserving attention for possible association with pain memory: They are related to cell-to-cell interaction, synaptogenesis, and neurogenesis.We suggest that lasting changes in expression of genes involved in the formation of new synapses and neurogenesis may contribute to the transition of acute pain to chronicity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Neurogenomic Laboratory Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. ryyukhan@zeus.bwh.harvard.edu

ABSTRACT

Background: Previous studies found that rats subjected to carrageenan injection develop hyperalgesia, and despite complete recovery in several days, they continue to have an enhanced hyperalgesic response to a new noxious challenge for more than 28d. The study's aim was to identify candidate genes that have a role in the formation of the long-term hyperalgesia-related imprint in the spinal cord. This objective was undertaken with the understanding that the long-lasting imprint of acute pain in the central nervous system may contribute to the transition of acute pain to chronicity.

Results: To analyze changes in gene expression when carrageenan-induced hyperalgesia has disappeared but propensity for the enhanced hyperalgesic response is still present, we determined the gene expression profile using oligo microarray in the lumbar part of the spinal cord in three groups of rats: 28d after carrageenan injection, 24h after injection (the peak of inflammation), and with no injection (control group). Out of 17,000 annotated genes, 356 were found to be differentially expressed compared with the control group at 28d, and 329 at 24h after carrageenan injection (both groups at p < 0.01). Among differentially expressed genes, 67 (39 in 28d group) were identified as being part of pain-related pathways, altered in different models of pain, or interacting with proteins involved in pain-related pathways. Using gene ontology (GO) classification, we have identified 3 functional classes deserving attention for possible association with pain memory: They are related to cell-to-cell interaction, synaptogenesis, and neurogenesis.

Conclusion: Despite recovery from inflammatory hyperalgesia, persistent changes in spinal cord gene expression may underlie the propensity for the enhanced hyperalgesic response. We suggest that lasting changes in expression of genes involved in the formation of new synapses and neurogenesis may contribute to the transition of acute pain to chronicity.

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Effect of carrageenan on noxious pressure threshold and paw volume. The carrageenan was injected in the plantar surface of the right paw (2%, 0.1 ml). Left Graph. Noxious pressure threshold was measured by Analgesia-Meter (Ugo Basile). Right Graph. Volume measured by a plethysmometer. Data expressed as mean ± SD. The threshold to noxious pressure in the right hindpaw, decreased after carrageenan injection, recovered the next day and was equal to the threshold in the left hindpaw for the whole period of observation (up to 28d).
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Figure 1: Effect of carrageenan on noxious pressure threshold and paw volume. The carrageenan was injected in the plantar surface of the right paw (2%, 0.1 ml). Left Graph. Noxious pressure threshold was measured by Analgesia-Meter (Ugo Basile). Right Graph. Volume measured by a plethysmometer. Data expressed as mean ± SD. The threshold to noxious pressure in the right hindpaw, decreased after carrageenan injection, recovered the next day and was equal to the threshold in the left hindpaw for the whole period of observation (up to 28d).

Mentions: Carrageenan injection into a rat's hind paw induces inflammation and hyperalgesia (Fig. 1). Inflammation measured as increased paw volume reaches its maximum 3–24h after injection. The differences in paw volume between the injected and contralateral paws are minimal after 5 days and completely disappear in 2 weeks (Fig. 1B). Injection-induced hyperalgesia disappears at 24h (Fig. 1A). However, as was shown in previous experiments, after recovery from hyperalgesia a repeated-crossover injection of carrageenan (in the opposite hindpaw) produced a more exaggerated response, resulting in profound distant hyperalgesia in the originally injected paw even 28d later [7]. In order to distinguish the acute changes induced by inflammation from long-term changes related to pain memory, we collected tissue samples both at 24h following injection, when the inflammation is still significant but there is no hyperalgesia, and at 28d, when as reported previously [7] there is no inflammation but enhanced response to pain stimulus, or "pain memory."


Persistent changes in spinal cord gene expression after recovery from inflammatory hyperalgesia: a preliminary study on pain memory.

Yukhananov R, Kissin I - BMC Neurosci (2008)

Effect of carrageenan on noxious pressure threshold and paw volume. The carrageenan was injected in the plantar surface of the right paw (2%, 0.1 ml). Left Graph. Noxious pressure threshold was measured by Analgesia-Meter (Ugo Basile). Right Graph. Volume measured by a plethysmometer. Data expressed as mean ± SD. The threshold to noxious pressure in the right hindpaw, decreased after carrageenan injection, recovered the next day and was equal to the threshold in the left hindpaw for the whole period of observation (up to 28d).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2315656&req=5

Figure 1: Effect of carrageenan on noxious pressure threshold and paw volume. The carrageenan was injected in the plantar surface of the right paw (2%, 0.1 ml). Left Graph. Noxious pressure threshold was measured by Analgesia-Meter (Ugo Basile). Right Graph. Volume measured by a plethysmometer. Data expressed as mean ± SD. The threshold to noxious pressure in the right hindpaw, decreased after carrageenan injection, recovered the next day and was equal to the threshold in the left hindpaw for the whole period of observation (up to 28d).
Mentions: Carrageenan injection into a rat's hind paw induces inflammation and hyperalgesia (Fig. 1). Inflammation measured as increased paw volume reaches its maximum 3–24h after injection. The differences in paw volume between the injected and contralateral paws are minimal after 5 days and completely disappear in 2 weeks (Fig. 1B). Injection-induced hyperalgesia disappears at 24h (Fig. 1A). However, as was shown in previous experiments, after recovery from hyperalgesia a repeated-crossover injection of carrageenan (in the opposite hindpaw) produced a more exaggerated response, resulting in profound distant hyperalgesia in the originally injected paw even 28d later [7]. In order to distinguish the acute changes induced by inflammation from long-term changes related to pain memory, we collected tissue samples both at 24h following injection, when the inflammation is still significant but there is no hyperalgesia, and at 28d, when as reported previously [7] there is no inflammation but enhanced response to pain stimulus, or "pain memory."

Bottom Line: Out of 17,000 annotated genes, 356 were found to be differentially expressed compared with the control group at 28d, and 329 at 24h after carrageenan injection (both groups at p < 0.01).Using gene ontology (GO) classification, we have identified 3 functional classes deserving attention for possible association with pain memory: They are related to cell-to-cell interaction, synaptogenesis, and neurogenesis.We suggest that lasting changes in expression of genes involved in the formation of new synapses and neurogenesis may contribute to the transition of acute pain to chronicity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Neurogenomic Laboratory Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. ryyukhan@zeus.bwh.harvard.edu

ABSTRACT

Background: Previous studies found that rats subjected to carrageenan injection develop hyperalgesia, and despite complete recovery in several days, they continue to have an enhanced hyperalgesic response to a new noxious challenge for more than 28d. The study's aim was to identify candidate genes that have a role in the formation of the long-term hyperalgesia-related imprint in the spinal cord. This objective was undertaken with the understanding that the long-lasting imprint of acute pain in the central nervous system may contribute to the transition of acute pain to chronicity.

Results: To analyze changes in gene expression when carrageenan-induced hyperalgesia has disappeared but propensity for the enhanced hyperalgesic response is still present, we determined the gene expression profile using oligo microarray in the lumbar part of the spinal cord in three groups of rats: 28d after carrageenan injection, 24h after injection (the peak of inflammation), and with no injection (control group). Out of 17,000 annotated genes, 356 were found to be differentially expressed compared with the control group at 28d, and 329 at 24h after carrageenan injection (both groups at p < 0.01). Among differentially expressed genes, 67 (39 in 28d group) were identified as being part of pain-related pathways, altered in different models of pain, or interacting with proteins involved in pain-related pathways. Using gene ontology (GO) classification, we have identified 3 functional classes deserving attention for possible association with pain memory: They are related to cell-to-cell interaction, synaptogenesis, and neurogenesis.

Conclusion: Despite recovery from inflammatory hyperalgesia, persistent changes in spinal cord gene expression may underlie the propensity for the enhanced hyperalgesic response. We suggest that lasting changes in expression of genes involved in the formation of new synapses and neurogenesis may contribute to the transition of acute pain to chronicity.

Show MeSH
Related in: MedlinePlus