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Table 2 Spinal cord stimulation exerts analgesia by activating specific receptor subtypes

From: Spinal cord stimulation in chronic pain: evidence and theory for mechanisms of action

Analgesia-Response To:

Neurotransmitter

Receptor Subtype

P-SCS

B-SCS

HF-SCS

DRG-S

5-HT

5-HT1:

5-HT2:

5-HT3:

5-HT4:

5-HT6:

5-HT7:

(Song et al., 2011)

(Barchini et al., 2012)

(Song et al., 2011; Barchini et al., 2012)

↑↑ (Song et al., 2011)

(Song et al., 2011)

(Song et al., 2011)

(Song et al., 2011)

   

GABA

GABAA:

GABAB:

(Duggan & Foong, 1985; Song et al., 2011; Barchini et al., 2012)

(Cui et al., 1996)

↑↑ (Song et al., 2009; Song et al., 2011; Cui et al., 1996; Barchini et al., 2012)

   

NE

α1 adrenergic:

α2 adrenergic:

β1 adrenergic:

β2 adrenergic:

(Barchini et al., 2012)

↑↑ (Barchini et al., 2012; Schechtmann et al., 2004)

(Barchini et al., 2012)

(Barchini et al., 2012)

   

Dopamine

D2

D3

(Barchini et al., 2012)

(Barchini et al., 2012)

   

ACh

M1 mAChR:

M2 mAChR:

M3 mAChR:

M4 mAChR:

nAChR:

(Schechtmann et al., 2008)

(Schechtmann et al., 2008; Song et al., 2008)

(Schechtmann et al., 2008)

↑↑ (Schechtmann et al., 2008; Song et al., 2008)

(Song et al., 2009)

(Schechtmann et al., 2008)

   
  1. Activation of specific receptor subtypes contributes to P-SCS mediated analgesia. Experiments used receptor antagonists and agonists to clarify the role of particular receptors to SCS-mediated analgesia. 5-HT3 receptor, GABAB receptor, α2 adrenergic receptor and M4 mAChR pathways were found to contribute to this analgesia to a greater extent than other receptor subtypes. An “up” arrow indicates that activation of that particular receptor subtype contributed to analgesia. ‘Double up’ arrows represent a greater increase and the predominant pathway. ‘Sideways’ arrows represent no contribution to analgesia. Acronyms: Glu (Glutamate), 5-HT (5-hydroxytryptamine, serotonin), GABA (Gamma-aminobutyric Acid), NE (Norepinephrine), ACh (Acetylcholine), 5-HT1 (5-hydroxytryptamine receptor 1), 5-HT2 (5-hydroxytryptamine receptor 2), 5-HT3 (5-hydroxytryptamine receptor 3), 5-HT4 (5-hydroxytryptamine receptor 4), 5-HT6 (5-hydroxytryptamine receptor 6), 5-HT7 (5-hydroxytryptamine receptor 7), GABAA (Gamma-aminobutyric Acid A Receptor), GABAB (Gamma-aminobutyric Acid B Receptor), α1 (Alpha 1 Adrenergic Receptor), α2 (Alpha 2 Adrenergic Receptor), β1 (Beta 1 Adrenergic Receptor), β2 (Beta 2 Adrenergic Receptor), D1 (Dopamine 1 Receptor), D2 (Dopamine 2 Receptor), M1 mAChR (Muscarinic 1 Acetylcholine Receptor), M2 mAChR (Muscarinic 2 Acetylcholine Receptor), M3 mAChR (Muscarinic 3 Acetylcholine Receptor), M4 mAChR (Muscarinic 4 Acetylcholine Receptor), nAChR (Nicotinic Acetylcholine Receptor)