Table 1 Synopsis of clinical studies using cellular therapies for chronic pain

Primary adrenal medullary/chromaffin tissue

Cadaveric adrenal medullary transplants into 5 subjects with intractable cancer pain

80% response rate with reduced demand for opioid analgesia

[38]

Allograft to lumbar in 2 subjects with chronic cancer pain

Clinical improvement with increase in CSF Met-enkephalin levels

[39]

Encapsulated bovine chromaffin cells implanted as a device in subarachnoid space of 7 subjects with chronic pain

Reduction of morphine requirement from 30-100% within a period of 41-176 days post-implantation

[43]

Phase II trial with allograft to CSF space in 15 subjects with cancer pain

Reduction of intra-thecal morphine dosage and increase in CSF Met-enkephalin levels

[44]

Bone marrow-MSC

Bone-marrow MSC co-cultured with autoimmune T-cells given to 2 human subjects with chronic SCI

Recovery of motor and sensory functions up to 8 spinal cord levels within 6 months

[45]

Open label case-control study with 64 subjects (44 as trial and 20 as control) using monthly intrathecal autologous MSC transplant for 6 months

No significant differences found in terms of ASIA score, 55.8% of treated subjects developed neuropathic pain

[46]

Three cycles of allogeneic MSC treated CD34 cells given over 14 months to a subject with incomplete SCI

Reduction of neuropathic pain by 70% and resumption of motor and sexual activities

[47]

Bone marrow transplant

Unmanipulated autologous bone marrow transplant to 20 subjects with complete SCI

Regime generally safe and feasible

[48]

Phase I/II open label trial with 35 subjects having complete SCI receiving autologous bone marrow with GM-CSF

Clinical improvement in 30.4% of subjects with no complication of tumour or neuropathic pain formation

[49]

Uncontrolled series in Ecuador with 52 subjects with SCI given bone marrow stem cells

Clinical improvements described

[50]

Phase I/II study with 297 patients with SCI receiving single unmanipulated autologous bone marrow cells

Regime relatively safe with improvement in motor/sensory functions in 1/3 subjects

[51]

Clinical pilot with 30 subjects with SCI receiving single dose of ex-vivo expanded bone marrow transplant

Clinical improvement in subjects with < 6 months injury, not sure if effects due to spontaneous recovery

[52]

Olfactory ensheathing cells (OEC)

Phase I/IIa study with 6 subjects with thoracic paraplegia receiving autologous OEC and followed up at 1 yr and 3 yrs

1 out of 6 subjects had mild clinical improvement

[53, 54]

Uncontrolled trial with 16 subjects receiving heterologous OEC from aborted foetuses

No improvement mentioned

[55]

Pilot study with seven subjects (ASIA class A) having olfactory mucosa autografts (OMA) into spinal cord lesions, later escalated to a prospective study with 20 subjects

Feasible and safe procedure with improvement with ASIA scores, bladder sensations and sphincter functions, with additional radiological improvements in the prospective study

[56, 57]

Pilot study with 5 subjects with chronic SCI receiving OMA

No significant improvement, development of syrinx in one subject and myelomalacia in other 4

[58]

Schwann cells

Pilot study with 4 subjects receiving autologous transplant from sural nerve cultures

Overall no adverse effects with improvement in only one subject

[59]

Anti-TNF-α

One report of current usage of etanercept in one subject with accident of T7 cord transection

Significant reduction of inflammation and motor improvement

[60]

Anti-Nogo-A

Phase I study with anti-Nogo-A given to > 50 subjects within 14 days of SCI

Still under evaluation

[61]