Table 2.
Effects of CeA manipulation on pain-related outcomes in different pain models
| Pain typea | Pain related outcomeb | Reference | |
|---|---|---|---|
| Nociceptive behavior | Affective/emotional | ||
| 1. CeA lesion | |||
| Naïve | - Reduced morphine-induced, stress-induced and conditioned hypoalgesia | [55, 56, 69] | |
| Formalin | - Reduced morphine-induced and conditioned hypoalgesia | - Decreased pain-induced CPA | [70–73] |
| Acetic acid | - Decreased pain-induced CPA | [72] | |
| 2. Injection of muscimol | |||
| Neuropathy | - Reduced mechanical hyperalgesia | - Decreased escape/avoidance | [74] |
| 3. Injection of NMDA antagonist | |||
| Neuropathy | - Decreased pain-induced CPA | [75] | |
| 4. Injection of group I mGluRs ligands | |||
| Naïve | - Agonist induced visceral and mechanical hypersensitivity | [76, 77] | |
| - Antagonist reduced visceral sensitivity | |||
| Formalin | - Antagonist reduced mechanical hypersensitivity | [77] | |
| Arthritis | - Antagonist reduced mechanical hypersensitivity | - Antagonist decreased vocalizations | [78] |
| Neuropathy | - Agonist increased, and antagonist decreased, pain-induced CPA | [75] | |
| 5. Injection of group III mGluRs agonists | |||
| Naïve | - Decreased mechanical sensitivity (mGluR7) | - Decreased vocalizations and anxiety | [79] |
| Arthritis | - Increased mechanical sensitivity (mGluR8) | - Increased vocalizations and anxiety | [79] |
| 6. Injection of cholinergic agonists | |||
| Naïve | - Decreased thermal sensitivity, reduced jaw opening reflex | - Decreased vocalizations | [63, 65, 66] |
| 7. Injection of noradrenergic α 2 ligands | |||
| Naïve | - Agonist induced mechanical and thermal hypoalgesia | [64, 80] | |
| - Antagonist reduced stress-induced thermal hypoalgesia | |||
| Acetic acid | - Agonist decreased pain-induced CPA | [81] | |
| 8. Injection of noradrenergic β antagonists | |||
| Acetic acid | - Decreased pain-induced CPA | [81] | |
| 9. Injection of CGRP receptor ligands | |||
| Naïve | - CGRP decreased mechanical and thermal reflexes | [59] | |
| Naïve | - CGRP increased mechanical reflexes | - CGRP increased vocalizations | [82] |
| Arthritis | - CGRP1 antagonist inhibited the enhanced reflex to mechanical stimulus | - CGRP1 antagonist decreased vocalizations | [83] |
| 10. Injection of CRF receptor ligands | |||
| Naïve | - CRF decreased mechanical and thermal sensitivity | [58] | |
| Naïve | - CRF increases mechanical sensitivity | - CRF increased vocalizations | [84] |
| Arthritis | - CRF1 antagonist reduced mechanical hypersensitivity | - CRF1 antagonist decreased vocalizations and anxiety | [85, 86] |
| 11. Injection of oxytocin, vasopressin, neurotensin, galanin | |||
| Naïve | - Decreased mechanical and/or thermal sensitivity | [57, 60–62] | |
| 12. Injection of opioid receptors ligands | |||
| Naïve | - Morphine and β-endorphin induced mechanical and thermal hypoalgesia | - Morphine decreased vocalizations | [47, 66] |
| 13. Corticosterone implants | |||
| Naïve | - Sensitized visceromotor reflexes to colorectal and urinary bladder distension and to somatic mechanical sensitivity | - Increased anxiety | [87–90] |
| 14. BDNF gene deletion in the PB-CeA pathway | |||
| Naïve | - Decreased morphine-induced mechanical and thermal hypoalgesia | [68] | |
| 15. Intracellular effectors | |||
| Naïve | - ERK activator induced mechanical hypersensitivity | [30] | |
| Formalin | - ERK activation inhibitor decreased mechanical hypersensitivity | [30, 31] | |
| Arthritis | - ERK activation inhibitor and PKA inhibitor decreased mechanical hypersensitivity | - ERK activation inhibitor and PKA inhibitor decreased vocalizations | [91] |
aPain type. naive nociceptive testing on naive animals; formalin: intraplantar injection of diluted formalin in hindpaw; acetic: intraperitoneal injection of acetic acid; arthritis: intraarticular injection of kaolin-caragenean in knee; neuropathy: compression or ligation of sciatic nerve or spinal root.
bPain related outcome. thermal sensitivity: latency of withdrawal or escape in tail-flick, hot-plate or Heargraves tests; mechanical sensitivity: latency or threshold to withdrawal in von Frey or Randall-Sellito tests; CPA: pain-induced conditioned place aversion; vocalizations: intensity/duration/threshold of vocalizations to electrical shock (naive) or mechanical compression of knee (naive, arthritis); anxiety: anxiety-like behavior in elevated plus maze test.