Ketamine does not produce relief of neuropathic pain in mice lacking the β-common receptor (CD131).

Swartjes M, Niesters M, Heij L, Dunne A, Aarts L, Hand CC, Kim HS, Brines M, Cerami A, Dahan A

PloS one1 Aug 2013Cited by 17 (Europe PMC)

PMID23936499PMCIDPMC3731332DOI10.1371/journal.pone.0071326PepBankPUB-23936499

Summary

Neuropathic pain (NP) is a debilitating condition associated with traumatic, metabolic, autoimmune and neurological etiologies. Although the triggers for NP are diverse, there are common underlying pathways, including activation of immune cells in the spinal cord and up-regulation of the N-methyl-D-aspartate receptor (NMDAR). Ketamine, a well-known NDMAR antagonist, reduces neuropathic pain in a sustained manner. Recent study has shown that the novel 11-amino acid peptide erythropoietin derivative ARA290 produces a similar, long-lasting relief of NP. Here, we show that both drugs also have similar effects on the expression of mRNA of the NMDAR, as well as that of microglia, astrocytes and chemokine (C-C motif) ligand 2, all-important contributors to the development of NP. Although the effects of ketamine and ARA 290 on NP and its molecular mediators suggest a common mechanism of action, ARA 290 has no affinity for the NMDAR and acts specifically via the innate repair receptor (IRR) involved in tissue protection. We speculated therefore, that the IRR might be critically involved in the action of ketamine on neuropathic pain. To evaluate this, we studied the effects of ketamine and ARA 290 on acute pain, side effects, and allodynia following a spared nerve injury model in mice lacking the β-common receptor (βcR), a structural component of the IRR. Ketamine (50 mg/kg) and ARA 290 (30 µg/kg) produced divergent effects on acute pain: ketamine produced profound antinociception accompanied with psychomotor side effects, but ARA290 did not, in both normal and knock out mice. In contrast, while both drugs were antiallodynic in WT mice, they had no effect on NP in mice lacking the βcR. Together, these results show that an intact IRR is required for the effective treatment of NP with either ketamine or ARA 290, but is not involved in ketamine's analgesic and side effects.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study8

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

01AnimalAnimal study (in vivo)Efficacy outcome
In normal and β-common receptor knockout mice, ARA290 did not produce antinociception in acute pain tests.
In plain wordsIn mice, ARA290 did not reduce acute pain, in both normal mice and mice lacking the β-common receptor.
Peptide
Cibinetide (ARA-290)
Outcome
No significant changeAcute pain (antinociception)
Study
mousen: not reported in source
Spared nerve injury; wild-type and β-common receptor knockout mice
Outcome group
Pain · Nervous system and cognition
Studied dose
30 μg/kgAs given in this study (mouse).
Source sentences
Summary
Ketamine (50 mg/kg) and ARA 290 (30 µg/kg) produced divergent effects on acute pain: ketamine produced profound antinociception accompanied with psychomotor side effects, but ARA290 did not, in both normal and knock out mice.
1 context sentence(design, population, supporting numbers)
Summary · context
To evaluate this, we studied the effects of ketamine and ARA 290 on acute pain, side effects, and allodynia following a spared nerve injury model in mice lacking the β-common receptor (βcR), a structural component of the IRR.
Show in the study text Report a problemFND-2393649901
02AnimalAnimal study (in vivo)Safety outcome
In normal and β-common receptor knockout mice, ARA290 did not produce psychomotor side effects.
In plain wordsIn mice, ARA290 did not cause movement or behavior side effects, in both normal mice and mice lacking the β-common receptor.
Peptide
Cibinetide (ARA-290)
Outcome
No significant changePsychomotor side effects
Study
mousen: not reported in source
Spared nerve injury; wild-type and β-common receptor knockout mice
Outcome group
Adverse events · Nervous system and cognition
Studied dose
30 μg/kgAs given in this study (mouse).
Source sentences
Summary
Ketamine (50 mg/kg) and ARA 290 (30 µg/kg) produced divergent effects on acute pain: ketamine produced profound antinociception accompanied with psychomotor side effects, but ARA290 did not, in both normal and knock out mice.
1 context sentence(design, population, supporting numbers)
Summary · context
To evaluate this, we studied the effects of ketamine and ARA 290 on acute pain, side effects, and allodynia following a spared nerve injury model in mice lacking the β-common receptor (βcR), a structural component of the IRR.
Show in the study text Report a problemFND-2393649902
03AnimalAnimal study (in vivo)Efficacy outcome
In wild-type mice with spared nerve injury, ARA290 was antiallodynic.
In plain wordsIn normal mice with nerve injury, ARA290 reduced pain from light touch.
Peptide
Cibinetide (ARA-290)
Outcome
DecreaseAllodynia in wild-type mice
Study
mousen: not reported in source
Spared nerve injury; wild-type mice
Outcome group
Pain · Nervous system and cognition
Studied dose
30 µg/kgAs given in this study (mouse).
Source sentences
Summary
while both drugs were antiallodynic in WT mice, they had no effect on NP in mice lacking the βcR.
1 context sentence(design, population, supporting numbers)
Summary · context
To evaluate this, we studied the effects of ketamine and ARA 290 on acute pain, side effects, and allodynia following a spared nerve injury model in mice lacking the β-common receptor (βcR), a structural component of the IRR.
Show in the study text Report a problemFND-2393649903
04AnimalAnimal study (in vivo)Efficacy outcome
In mice lacking the β-common receptor, ARA290 had no effect on neuropathic pain after spared nerve injury.
In plain wordsIn mice lacking the β-common receptor, ARA290 did not reduce nerve-injury pain.
Peptide
Cibinetide (ARA-290)
Outcome
No significant changeNeuropathic pain in β-common receptor knockout mice
Study
mousen: not reported in source
Spared nerve injury; β-common receptor knockout mice
Outcome group
Pain · Nervous system and cognition
Studied dose
30 µg/kgAs given in this study (mouse).
Source sentences
Summary
they had no effect on NP in mice lacking the βcR.
1 context sentence(design, population, supporting numbers)
Summary · context
To evaluate this, we studied the effects of ketamine and ARA 290 on acute pain, side effects, and allodynia following a spared nerve injury model in mice lacking the β-common receptor (βcR), a structural component of the IRR.
Show in the study text Report a problemFND-2393649904
05AnimalAnimal study (in vivo)Mechanism
In mice, ARA290 affected NMDA receptor mRNA expression, with an effect similar to that of ketamine; the direction is not stated.
In plain wordsIn mice, ARA290 changed NMDA receptor gene activity in a way similar to ketamine; the abstract does not say which way.
Peptide
Cibinetide (ARA-290)
Outcome
Direction not reportedNMDA receptor mRNA expression
Study
mousen: not reported in source
Spared nerve injury; wild-type and β-common receptor knockout mice
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
Here, we show that both drugs also have similar effects on the expression of mRNA of the NMDAR, as well as that of microglia, astrocytes and chemokine (C-C motif) ligand 2, all-important contributors to the development of NP.
1 context sentence(design, population, supporting numbers)
Summary · context
To evaluate this, we studied the effects of ketamine and ARA 290 on acute pain, side effects, and allodynia following a spared nerve injury model in mice lacking the β-common receptor (βcR), a structural component of the IRR.
Show in the study text Report a problemFND-2393649905
06AnimalAnimal study (in vivo)Mechanism
In mice, ARA290 affected microglia mRNA expression, with an effect similar to that of ketamine; the direction is not stated.
In plain wordsIn mice, ARA290 changed gene activity of microglia, immune cells of the nervous system, like ketamine did; the direction is not stated.
Peptide
Cibinetide (ARA-290)
Outcome
Direction not reportedMicroglia mRNA expression
Study
mousen: not reported in source
Spared nerve injury; wild-type and β-common receptor knockout mice
Outcome group
Inflammation markers · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
Here, we show that both drugs also have similar effects on the expression of mRNA of the NMDAR, as well as that of microglia, astrocytes and chemokine (C-C motif) ligand 2, all-important contributors to the development of NP.
1 context sentence(design, population, supporting numbers)
Summary · context
To evaluate this, we studied the effects of ketamine and ARA 290 on acute pain, side effects, and allodynia following a spared nerve injury model in mice lacking the β-common receptor (βcR), a structural component of the IRR.
Show in the study text Report a problemFND-2393649906
07AnimalAnimal study (in vivo)Mechanism
In mice, ARA290 affected astrocyte mRNA expression, with an effect similar to that of ketamine; the direction is not stated.
In plain wordsIn mice, ARA290 changed gene activity of astrocytes, support cells in the nervous system, like ketamine did; the direction is not stated.
Peptide
Cibinetide (ARA-290)
Outcome
Direction not reportedAstrocyte mRNA expression
Study
mousen: not reported in source
Spared nerve injury; wild-type and β-common receptor knockout mice
Outcome group
Inflammation markers · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
Here, we show that both drugs also have similar effects on the expression of mRNA of the NMDAR, as well as that of microglia, astrocytes and chemokine (C-C motif) ligand 2, all-important contributors to the development of NP.
1 context sentence(design, population, supporting numbers)
Summary · context
To evaluate this, we studied the effects of ketamine and ARA 290 on acute pain, side effects, and allodynia following a spared nerve injury model in mice lacking the β-common receptor (βcR), a structural component of the IRR.
Show in the study text Report a problemFND-2393649907
08AnimalAnimal study (in vivo)Mechanism
In mice, ARA290 affected CCL2 mRNA expression, with an effect similar to that of ketamine; the direction is not stated.
In plain wordsIn mice, ARA290 changed gene activity of the inflammation signal CCL2, like ketamine did; the direction is not stated.
Peptide
Cibinetide (ARA-290)
Outcome
Direction not reportedCCL2 mRNA expression
Study
mousen: not reported in source
Spared nerve injury; wild-type and β-common receptor knockout mice
Outcome group
Inflammation markers · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
Here, we show that both drugs also have similar effects on the expression of mRNA of the NMDAR, as well as that of microglia, astrocytes and chemokine (C-C motif) ligand 2, all-important contributors to the development of NP.
1 context sentence(design, population, supporting numbers)
Summary · context
To evaluate this, we studied the effects of ketamine and ARA 290 on acute pain, side effects, and allodynia following a spared nerve injury model in mice lacking the β-common receptor (βcR), a structural component of the IRR.
Show in the study text Report a problemFND-2393649908

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.

Version 2Current
9 Oct 2026, 19:08 UTC
Study results updated
Version 1
9 Oct 2026, 03:13 UTC
First added · source update from Europe PMC

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