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Study · Animal study (in vivo) · rat · 2014

6 results

ARA 290, a peptide derived from the tertiary structure of erythropoietin, produces long-term relief of neuropathic pain coupled with suppression of the spinal microglia response.

Swartjes M, van Velzen M, Niesters M, Aarts L, Brines M, Dunne A, Cerami A, Dahan A

Molecular pain16 Feb 2014Cited by 28 (Europe PMC)

PMID24529189 (opens in a new tab)PMCIDPMC3928087 (opens in a new tab)DOI10.1186/1744-8069-10-13 (opens in a new tab)PepBankPUB-24529189
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Summary

BackgroundNeuropathic pain is a difficult to treat disorder arising from central or peripheral nervous system lesions. The etiology of neuropathic pain consists of several overlapping pathways converging into an exaggerated pain state with symptoms such as allodynia and hyperalgesia. One of these pathways involves activation of spinal cord microglia and astrocytes, which drive and maintain the inflammatory response following the lesion. These cells are a potential target for drugs for neuropathic pain relief. In this current study, we investigated the dose-effect relationship of the tissue protective peptide ARA 290, derived from the tertiary structure of erythropoietin, on allodynia and concurrent spinal cord microglia and astrocytes.ResultsFollowing a spared nerve injury in rats, vehicle or ARA290 (administered in either one of 4 doses: 3, 10, 30 and 60 μg/kg) was administered on days 1, 3, 6, 8 and 10. ARA290 exerted a dose-response effect by significantly reducing mechanical allodynia up to 20 weeks when compared to vehicle. The reduction of cold allodynia was significant up to 20 weeks for the doses 3, 10, 30 and 60 μg/kg when compared to vehicle. The effect 10 and 30 μg/kg ARA290 and vehicle on the microglia response (iba-1-immunoreactivity, iba-1-IR) and astrocyte reaction (GFAP-immunoreactivity, GFAP-IR) was investigated in animals surviving 2 (group 1) or 20 (group 2) weeks following lesion or sham surgery. In group 1, significant microglia reactivity was observed in the L5 segment of the spinal cord of animals treated with vehicle when compared to sham operated, while animals treated with 10 or 30 μg/kg did not show a increase. In group 2, a more widespread and increased microglia reactivity was observed for animals treated with 0 and 10 μg/kg when compared to sham operated animals, indicated by involvement of more spinal cord segments and higher iba-1-IR. Animals treated with 30 μg/kg did not show increased microglia reactivity. No difference in astrocyte reaction was observed.ConclusionsThe erythropoietin-analogue ARA290 dose-dependently reduced allodynia coupled to suppression of the spinal microglia response, suggestive of a mechanistic link between ARA290-induced suppression of central inflammation and relief of neuropathic pain symptoms.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study6

6 results from studies that gave the peptide. No result from this study comes from people.

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In rats with spared nerve injury, ARA290 reduced mechanical allodynia in a dose-response manner for up to 20 weeks compared with vehicle.

    In plain wordsIn rats with nerve injury, ARA290 reduced pain from light touch for up to 20 weeks, compared with vehicle.

    Peptide
    Cibinetide (ARA-290)
    Outcome
    DecreaseMechanical allodynia
    Study

    ratn: not reported in source

    Spared nerve injury
    Comparator
    Vehicle
    Outcome group
    Pain · Nervous system and cognition
    Studied dose
    3, 10, 30 and 60 μg/kg · Days 1, 3, 6, 8 and 10As given in this study (rat).

    Source sentences

    Summary
    ARA290 exerted a dose-response effect by significantly reducing mechanical allodynia up to 20 weeks when compared to vehicle.
    1 context sentence
    Summary · context
    Following a spared nerve injury in rats, vehicle or ARA290 (administered in either one of 4 doses: 3, 10, 30 and 60 μg/kg) was administered on days 1, 3, 6, 8 and 10.
  2. 02AnimalAnimal study (in vivo)Efficacy outcome

    In rats with spared nerve injury, ARA290 at 3, 10, 30 and 60 μg/kg reduced cold allodynia for up to 20 weeks compared with vehicle.

    In plain wordsIn rats with nerve injury, ARA290 reduced pain from cold for up to 20 weeks, compared with vehicle.

    Peptide
    Cibinetide (ARA-290)
    Outcome
    DecreaseCold allodynia
    Study

    ratn: not reported in source

    Spared nerve injury
    Comparator
    Vehicle
    Outcome group
    Pain · Nervous system and cognition
    Studied dose
    3, 10, 30 and 60 μg/kg · Days 1, 3, 6, 8 and 10As given in this study (rat).

    Source sentences

    Summary
    The reduction of cold allodynia was significant up to 20 weeks for the doses 3, 10, 30 and 60 μg/kg when compared to vehicle.
    1 context sentence
    Summary · context
    Following a spared nerve injury in rats, vehicle or ARA290 (administered in either one of 4 doses: 3, 10, 30 and 60 μg/kg) was administered on days 1, 3, 6, 8 and 10.
  3. 03AnimalAnimal study (in vivo)Mechanism

    In rats 2 weeks after spared nerve injury, ARA290 at 10 or 30 μg/kg prevented the increase in L5 spinal microglia reactivity seen with vehicle.

    In plain wordsIn rats with nerve injury, ARA290 stopped the rise in spinal cord immune-cell activity that vehicle-treated rats showed at 2 weeks.

    Peptide
    Cibinetide (ARA-290)
    Outcome
    DecreaseSpinal microglia reactivity at 2 weeks (iba-1-IR, L5 segment)
    Study

    ratn: not reported in source

    Spared nerve injury
    Comparator
    Vehicle
    Outcome group
    Inflammation markers · Nervous system and cognition
    Studied dose
    10 and 30 μg/kg · Days 1, 3, 6, 8 and 10As given in this study (rat).

    Source sentences

    Summary
    In group 1, significant microglia reactivity was observed in the L5 segment of the spinal cord of animals treated with vehicle when compared to sham operated, while animals treated with 10 or 30 μg/kg did not show a increase.
    2 context sentences
    Summary · context
    The effect 10 and 30 μg/kg ARA290 and vehicle on the microglia response (iba-1-immunoreactivity, iba-1-IR) and astrocyte reaction (GFAP-immunoreactivity, GFAP-IR) was investigated in animals surviving 2 (group 1) or 20 (group 2) weeks following lesion or sham surgery.
    Summary · context
    Following a spared nerve injury in rats, vehicle or ARA290 (administered in either one of 4 doses: 3, 10, 30 and 60 μg/kg) was administered on days 1, 3, 6, 8 and 10.
  4. 04AnimalAnimal study (in vivo)Mechanism

    In rats 20 weeks after spared nerve injury, ARA290 at 10 μg/kg did not prevent widespread, increased spinal microglia reactivity versus sham-operated animals.

    In plain wordsIn rats with nerve injury, the lower ARA290 dose of 10 μg/kg did not stop the rise in spinal cord immune-cell activity at 20 weeks.

    Peptide
    Cibinetide (ARA-290)
    Outcome
    No significant changeSpinal microglia reactivity at 20 weeks, 10 μg/kg
    Study

    ratn: not reported in source

    Spared nerve injury
    Comparator
    Sham-operated animals
    Outcome group
    Inflammation markers · Nervous system and cognition
    Studied dose
    10 μg/kg · Days 1, 3, 6, 8 and 10As given in this study (rat).

    Source sentences

    Summary
    In group 2, a more widespread and increased microglia reactivity was observed for animals treated with 0 and 10 μg/kg when compared to sham operated animals, indicated by involvement of more spinal cord segments and higher iba-1-IR.
    2 context sentences
    Summary · context
    The effect 10 and 30 μg/kg ARA290 and vehicle on the microglia response (iba-1-immunoreactivity, iba-1-IR) and astrocyte reaction (GFAP-immunoreactivity, GFAP-IR) was investigated in animals surviving 2 (group 1) or 20 (group 2) weeks following lesion or sham surgery.
    Summary · context
    Following a spared nerve injury in rats, vehicle or ARA290 (administered in either one of 4 doses: 3, 10, 30 and 60 μg/kg) was administered on days 1, 3, 6, 8 and 10.
  5. 05AnimalAnimal study (in vivo)Mechanism

    In rats 20 weeks after spared nerve injury, ARA290 at 30 μg/kg did not show increased spinal microglia reactivity.

    In plain wordsIn rats with nerve injury, ARA290 at 30 μg/kg kept spinal cord immune-cell activity from rising at 20 weeks.

    Peptide
    Cibinetide (ARA-290)
    Outcome
    No significant changeSpinal microglia reactivity at 20 weeks, 30 μg/kg
    Study

    ratn: not reported in source

    Spared nerve injury
    Comparator
    Sham-operated animals
    Outcome group
    Inflammation markers · Nervous system and cognition
    Studied dose
    30 μg/kg · Days 1, 3, 6, 8 and 10As given in this study (rat).

    Source sentences

    Summary
    Animals treated with 30 μg/kg did not show increased microglia reactivity.
    2 context sentences
    Summary · context
    The effect 10 and 30 μg/kg ARA290 and vehicle on the microglia response (iba-1-immunoreactivity, iba-1-IR) and astrocyte reaction (GFAP-immunoreactivity, GFAP-IR) was investigated in animals surviving 2 (group 1) or 20 (group 2) weeks following lesion or sham surgery.
    Summary · context
    Following a spared nerve injury in rats, vehicle or ARA290 (administered in either one of 4 doses: 3, 10, 30 and 60 μg/kg) was administered on days 1, 3, 6, 8 and 10.
  6. 06AnimalAnimal study (in vivo)Mechanism

    In rats with spared nerve injury, no difference in astrocyte reaction (GFAP-IR) was observed with ARA290.

    In plain wordsIn rats with nerve injury, ARA290 did not change the reaction of astrocytes, a type of support cell in the spinal cord.

    Peptide
    Cibinetide (ARA-290)
    Outcome
    No significant changeSpinal astrocyte reaction (GFAP-IR)
    Study

    ratn: not reported in source

    Spared nerve injury
    Comparator
    Vehicle
    Outcome group
    Inflammation markers · Nervous system and cognition
    Studied dose
    10 and 30 μg/kg · Days 1, 3, 6, 8 and 10As given in this study (rat).

    Source sentences

    Summary
    No difference in astrocyte reaction was observed.
    2 context sentences
    Summary · context
    The effect 10 and 30 μg/kg ARA290 and vehicle on the microglia response (iba-1-immunoreactivity, iba-1-IR) and astrocyte reaction (GFAP-immunoreactivity, GFAP-IR) was investigated in animals surviving 2 (group 1) or 20 (group 2) weeks following lesion or sham surgery.
    Summary · context
    Following a spared nerve injury in rats, vehicle or ARA290 (administered in either one of 4 doses: 3, 10, 30 and 60 μg/kg) was administered on days 1, 3, 6, 8 and 10.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    9 Oct 2026, 19:08 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 03:13 UTC

    First added · source update from Europe PMC

Subjects

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