Impaired nocifensive behaviours and mechanical hyperalgesia, but enhanced thermal allodynia in pituitary adenylate cyclase-activating polypeptide deficient mice

K. Sándor, V. Kormos, B. Botz, A. Imreh, K. Bölcskei, B. Gaszner, A. Markovics, J. Szolcsányi, N. Shintani, H. Hashimoto, A. Baba, D. Reglodi, Z. Helyes

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38) and its receptors (PAC1 and VPAC) have been shown in the spinal dorsal horn, dorsal root ganglia and sensory nerve terminals. Data concerning the role of PACAP in central pain transmission are controversial and we have recently published its divergent peripheral effects on nociceptive processes.The aim of the present study was to investigate acute somatic and visceral nocifensive behaviours, partial sciatic nerve ligation-evoked chronic neuropathic, as well as resiniferatoxin-induced inflammatory thermal and mechanical hyperalgesia in PACAP deficient (PACAP-/-) mice to elucidate its overall function in pain transmission. Neuronal activation was investigated with c-Fos immunohistochemistry.Paw lickings in the early (0-5min) and late (20-45min) phases of the formalin test were markedly reduced in PACAP-/- mice. Acetic acid-evoked abdominal contractions referring to acute visceral chemonociception was also significantly attenuated in PACAP knockout animals. In both models, the excitatory role of PACAP was supported by markedly greater c-Fos expression in the periaqueductal grey and the somatosensory cortex. In PACAP-deficient animals neuropathic mechanical hyperalgesia was absent, while c-Fos immunopositivity 20days after the operation was significantly higher. In this chronic model, these neurons are likely to indicate the activation of secondary inhibitory pathways. Intraplantarly injected resiniferatoxin-evoked mechanical hyperalgesia involving both peripheral and central processes was decreased, but thermal allodynia mediated by only peripheral mechanisms was increased in PACAP-/- mice.These data clearly demonstrate an overall excitatory role of PACAP in pain transmission originating from both exteroceptive and interoceptive areas, it is also involved in central sensitization. This can be explained by the signal transduction mechanisms of its identified receptors, both PAC1 and VPAC activation leads to neuronal excitation. In contrast, it is an inhibitory mediator at the level of the peripheral sensory nerve endings and decreases their sensitization to heat with presently unknown mechanisms.

Original languageEnglish
Pages (from-to)363-371
Number of pages9
JournalNeuropeptides
Volume44
Issue number5
DOIs
Publication statusPublished - Oct 2010

Fingerprint

Pituitary Adenylate Cyclase-Activating Polypeptide
Hyperalgesia
Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
Pain
Central Nervous System Sensitization
Periaqueductal Gray
Somatosensory Cortex
Spinal Ganglia
Sensory Receptor Cells
Sciatic Nerve
Pain Measurement
Peripheral Nerves
Acetic Acid
Ligation
Signal Transduction
Hot Temperature
Immunohistochemistry

Keywords

  • C-Fos immunohistochemistry
  • Formalin test
  • Mechanical hyperalgesia
  • Neuropathy
  • Resiniferatoxin
  • Thermal allodynia
  • Writhing test

ASJC Scopus subject areas

  • Endocrinology
  • Neurology
  • Cellular and Molecular Neuroscience
  • Endocrine and Autonomic Systems

Cite this

Impaired nocifensive behaviours and mechanical hyperalgesia, but enhanced thermal allodynia in pituitary adenylate cyclase-activating polypeptide deficient mice. / Sándor, K.; Kormos, V.; Botz, B.; Imreh, A.; Bölcskei, K.; Gaszner, B.; Markovics, A.; Szolcsányi, J.; Shintani, N.; Hashimoto, H.; Baba, A.; Reglodi, D.; Helyes, Z.

In: Neuropeptides, Vol. 44, No. 5, 10.2010, p. 363-371.

Research output: Contribution to journalArticle

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AU - Markovics, A.

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