Pain-related behaviors and neurochemical alterations in mice expressing sickle hemoglobin

Modulation by cannabinoids

Divyanshoo R. Kohli, Yunfang Li, Sergey Khasabov, Pankaj Gupta, Lois J. Kehl, Marna E Ericson, Julia Nguyen, Vinita Gupta, Robert P Hebbel, Donald A Simone, Kalpna Gupta

Research output: Contribution to journalArticle

96 Citations (Scopus)

Abstract

Sickle cell disease causes severe pain. We examined pain-related behaviors, correlative neurochemical changes, and analgesic effects of morphine and cannabinoids in transgenic mice expressing human sickle hemoglobin (HbS). Paw withdrawal threshold and withdrawal latency (to mechanical and thermal stimuli, respectively) and grip force were lower in homozygous and hemizygous Berkley mice (BERK and hBERK1, respectively) compared with control mice expressing human hemoglobin A (HbA-BERK), indicating deep/musculoskeletal and cutaneous hyperalgesia. Peripheral nerves and blood vessels were structurally altered in BERK and hBERK1 skin, with decreased expression of μ opioid receptor and increased calcitonin gene-related peptide and substance P immunoreactivity. Activators of neuropathic and inflammatory pain (p38 mitogen-activated protein kinase, STAT3, and mitogen-activated protein kinase/extracellular signal-regulated kinase) showed increased phosphorylation, with accompanying increase in COX-2, interleukin-6, and Toll-like receptor 4 in the spinal cord of hBERK1 compared with HbA-BERK. These neurochemical changes in the periphery and spinal cord may contribute to hyperalgesia in mice expressing HbS. In BERK and hBERK1, hyperalgesia was markedly attenuated by morphine and cannabinoid receptor agonist CP 55940. We show that mice expressing HbS exhibit characteristics of pain observed in sickle cell disease patients, and neurochemical changes suggestive of nociceptor and glial activation. Importantly, cannabinoids attenuate pain in mice expressing HbS.

Original languageEnglish (US)
Pages (from-to)456-465
Number of pages10
JournalBlood
Volume116
Issue number3
DOIs
StatePublished - Jul 22 2010

Fingerprint

Sickle Hemoglobin
Cannabinoids
Modulation
Cannabinoid Receptor Agonists
Hyperalgesia
Hemoglobin A
Pain
Toll-Like Receptor 4
Phosphorylation
Calcitonin Gene-Related Peptide
mu Opioid Receptor
Extracellular Signal-Regulated MAP Kinases
Blood vessels
Opioid Receptors
p38 Mitogen-Activated Protein Kinases
Substance P
Mitogen-Activated Protein Kinases
Morphine
Analgesics
Sickle Cell Anemia

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Pain-related behaviors and neurochemical alterations in mice expressing sickle hemoglobin : Modulation by cannabinoids. / Kohli, Divyanshoo R.; Li, Yunfang; Khasabov, Sergey; Gupta, Pankaj; Kehl, Lois J.; Ericson, Marna E; Nguyen, Julia; Gupta, Vinita; Hebbel, Robert P; Simone, Donald A; Gupta, Kalpna.

In: Blood, Vol. 116, No. 3, 22.07.2010, p. 456-465.

Research output: Contribution to journalArticle

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