Table 1.

Primary afferent transducers

Transducer	Evidence	Sensitization	Ref.
Mechanical
ASIC1	Visceral afferents (↑ sensitivity in KO).	No published data regarding sensitization.	76
ASIC2	Visceral afferents (↑,↓, ↔ sensitivity in KO, afferent type-specific).	No published data.	76
ASIC3	Visceral afferents (↓ sensitivity in KO). Cutaneous afferents (↑,↓, ↔ sensitivity in KO).	Required for sensitization of colonic, muscle, joint nociceptors.	76
Cav3.2	Role in mechanosensitivity of down (fine) hair.	Target of acute modulation. Knock-down ↓ injury-induced hypersensitivity.	77
TRPV1	Role in response to hollow organ distension (↓ sensitivity in KO).	Block central channels ↓ mechanical hyperalgesia.	78
TRPV4	Direct activation by osmotic challenge, ↑ sensitivity with activation, ↓ sensitivity with block, knock down or KO.	Visceral, cutaneous hypersensitivity in inflammation and nerve injury.	79
TRPA1	Cutaneous afferents (↑,↓, ↔ sensitivity in KO, ↓ sensitivity with block). Visceral afferents (↓ sensitivity of subpopulations).	↑ with inflammation, ↓ mechanical hypersensitivity with block and KO in somatic and visceral afferents.	40,80
TRAAK	Direct activation by mechanical stimuli.	No published data.	43
TREK1/2	Direct activation by mechanical stimuli, ↑ sensitivity in KO.	↑ inflammatory hyperalgesia, potential role in neuropathic pain.	81,82
P2X3	Indirect activation through ATP release from epithelial cells, ↓ response to hollow organ distension in knock-down and KO.	Pro-nociceptive role in visceral and somatic pain associated with inflammation and nerve injury.	83
Thermal
TRAAK/TREK-1	Directly activated by heating, closed by cooling; ↑ response to cold in KO.	No published data.	84
NaV1.8	Resistant to cold-induced inactivation. Indirectly essential for cold transduction.	No published data.	34
TRPA1	Direct activation by cold stimulus, ↓ cold sensitivity in some but not all KO studies.	Role in cold sensitivity following sensitization.	85–87
TRPM8	Direct activation by cold stimulus, ↓ cold sensitivity in KO.	Role in increased cold sensitivity after injury (KO studies).	88,89
TRPV3	Direct activation by warm stimulus (presence in afferent is controversial).	‘Selective activation’ with farnesyl pyrophosphate increases nociceptive behavior.	90
TRPV4	Direct activation by warm stimulus.	More prominent role in mechanotransduction.	91
TRPV1	Direct activation by heat stimulus.	Multiple lines of evidence that TRPV1 is essential for thermal hyperalgesia associated with most types of tissue injury.	45
TRPV2	Direct activation by heat stimulus, but role in nociceptive processing remains controversial.	No published data	38
Chemical (ionotropic onlya)
ASIC1-4	Direct activation by protons.	Role in ischemia-induced pain, muscle hypersensitivity.	45
TRAAK/TREK	Channel activity influenced by a number of endogenous mediators such as protons and acachidonic acid.	No published data.	43,81
TRPV1	Direct activation, modulation by protons, fatty acids, arachidonic acid derivatives, vanilloids.	Most compelling evidence for a role in thermal hypersensitivity.	45
TRPA1	Direct activation by a number of compounds (mustard oil, cinimaldehyde, acrolein, formalin).	Essential for chemical-induced hypersensitivity.	85
TRPM8	Direct activation by menthol.	Most compelling evidence for role in cold hypersensitivity.	88
P2X1-6	Direct activation by ATP (prominent role for P2X2/3).	Evidence for role in pain and hypersensitivity associated with injury to many different tissue types.	92
5-HT3	Direct activation by serotonin, role in subset of nociceptive afferents.	Most prominent role in visceral pain.	93
nACh (multiple subunits are present in DRG)	Direct activation by acetylcholine (ACh).	Increased subunit expression with injury, increased peripheral ACh with injury, may have pronociceptive role in periphery, antinociceptive role in central terminals.	94
Glutamate (GluR1-5, NR1-2)	Direct activation by glutamate and subtype-specific agonists.	Evidence for peripheral role in pain, but most compelling evidence for role on central terminals.	95
GABA (multiple subunits are present in DRG)	Direct activation by GABA and subunit-specific agonists.	May be inhibitory or excitatory depending on chloride equilibrium potential at receptor.	96

↑, ↓ and ↔ represent, respectively, increase, decrease and no change. KO, knockout.

^aBecause of the large number of metabotropic receptors present in sensory neurons, they have not been included in the table. Bold entries have the most compelling evidence suggesting that selective block of the channel may have therapeutic efficacy in pain.